以HDL受体SR-BI基因3'UTR为靶点的microRNA和小分子化合物的发现及作用机制研究
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摘要
过去几十年,人类心血管健康问题得到有效改善,但是,心血管疾病依然是世界范围内最主要的致残和致死性疾病。心血管疾病患者经济负担沉重,社会活动受到限制,生活质量严重下降,更有甚者饱受长期残疾之苦,容易导致过早死亡。采取有效措施,促进心血管疾病的预防和治疗有重大的临床和社会效益。动脉粥样硬化是大多数心血管疾病的病理学基础,所以急需发展新的更好的抗动脉粥样硬化策略。大量流行病学研究表明,血浆高密度脂蛋白浓度与动脉粥样硬化发病风险呈负相关。高密度脂蛋白介导的胆固醇从外周组织到肝脏的运输,称为胆固醇的逆向转运,是维持体内胆固醇平衡的一个主要途径。选择性胆固醇的摄取是受体介导的高密度脂蛋白胆固醇酯直接转运的主要机制。SR-BI作为高密度脂蛋白受体介导肝脏和类固醇合成组织选择性摄取血浆高密度脂蛋白胆固醇。肝脏SR-BI过表达能有效促进胆固醇逆转运,减少动脉粥样硬化。因此,SR-BI被认为具有明显的抗动脉粥样硬化功能。SR-BI可能成为预防或治疗动脉粥样硬化性疾病的重要靶点。
在本研究的第一部分,我们考察了参与肝脏SR-BI基因转录后调控和高密度脂蛋白胆固醇选择性摄取调节机制的microRNA。肝细胞HepG2中,miR-185、 miR-96和miR-223能显著抑制SR-BI表达,并且分别以31.9%(P<0.001)、23.9%(P<0.05)和15.4%(P<0.05)的比例降低DiI-HDL摄取。它们的反义寡核苷酸抑制剂呈现相反的效应。作用位点缺失后,miR-96, miR-185和miR-223失去调节功能,这进一步确证了它们对SR-BI的调节作用。此外,这几个microRNA还能以协同效应的方式直接作用于SR-BI基因mRNA3'UTR序列。更值得关注的是,高脂饲料喂养的ApoE基因敲除小鼠miR-96和miR-185与SR-BI的表达呈截然相反的变化,SR-BI表达增加,而miR-96和miR-185的表达水平降低。这些实验数据表明,人类肝细胞中,miR-185、miR-96和miR-223可以通过抑制SR-BI的表达来抑制HDL-C选择性摄取。这一发现是肝脏SR-BI基因表达调控的新模式,同时也揭示了microRNA参与胆固醇代谢调节的新机制。
在本研究的第二部分,我们发现和确证了几个具有增强SR-BI基因mRNA稳定性功能的小分子化合物,并明确了它们调节SR-BI表达和功能的作用。我们将人SR-BI基因mRNA3'UTR序列构建在荧光素酶报告基因下游,建立以稳定转染HepG2细胞为基础的高通量筛选模型,筛选3'UTR序列相关的能够显著增强SR-BI基因mRNA稳定性的小分子化合物。筛选条件的优化和模型参数的评价表明该模型符合高通量筛选的要求,合理有效,可用于微生物次级代谢产物库和化合物库的大规模高通量筛选。通过对国家新药(微生物)筛选中心化合物库提供的25755个化合物的多轮筛选,获得6个阳性化合物,筛选阳性率0.23‰。获得的六个阳性化合物均能有效提高肝细胞SR-BI表达和DiI-HDL选择性摄取。进一步研究表明,化合物5172B-41和5238B-63能够有效延长肝细胞SR-BI基因mRNA半衰期,提高SR-BI基因mRNA水平和蛋白表达水平,从而明确了它们增强肝细胞SR-BI基因mRNA稳定性的功能。化合物5172B-41和5238B-63以时间依赖性和剂量依赖性的方式影响SR-BI基因表达和肝细胞对DiI-HDL的选择性摄取。构效关系分析为进一步获得更好活性的候选化合物提供了很多有益参考。本研究获得的阳性小分子化合物具有明确的作用靶点,有可能发展成为新型心血管疾病治疗候选药物或先导化合物,并有助于对SR-BI基因转录后调控机制进行深入研究。
Despite significant improvements in the cardiovascular health in recent decades, cardiovascular disease (CVD) continues to be the leading cause of morbidity and mortality worldwide. It imposes a significant burden in terms of costs, premature death, long-term disability, restricted social functioning and reduction in patient's quality of life. Effective interventions in cardiovascular disease treatment and prevention have long-term clinical and economic consequences. Since atherosclerosis is the central biological process underlying most cardiovascular diseases, new and better anti-atherosclerotic strategies are required. Plasma concentrations of high density lipoprotein (HDL) have been known to inversely correlate with risk for atherosclerosis. Bulk transport of HDL cholesterol from the peripheral tissues to the liver is a major pathway, termed reverse cholesterol transport, responsible for maintaining whole body cholesterol homeostasis. A key mechanism of receptor-mediated direct delivery of HDL cholesteryl esters to the liver and steroidogenic tissues is selective cholesterol uptake. Scavenger receptor class B type I (SR-BI), HDL receptor, mediates the selective uptake of plasma HDL cholesterol by the liver and steroidogenic tissues. Increasing the expression of hepatic SR-BI promotes reverse cholesterol transport and reduces atherosclerosis. Therefore, SR-BI has considerable antiatherogenic capacity. SR-BI may become an attractive target for prevention of or therapeutic intervention in a variety of human diseases.
In the first part of this study, the potential involvement of microRNAs in posttranscriptional regulation of hepatic SR-BI and selective HDL-C uptake was investigated. The level of SR-BI expression was repressed by miR-185, miR-96, and miR-223, while the uptake of DiI-HDL was decreased by31.9%(P<0.001),23.9%(P <0.05), and15.4%(P<0.05), respectively, in HepG2cells. The inhibition of these microRNAs by their anti-microRNAs had opposite effects in these hepatic cells. The critical effect of miR-185was further validated by the loss of regulation in constructs with mutated miR-96, miR-185and miR-223target sites. In addition, these microRNAs directly targeted the3'untranslated region (UTR) of SR-BI with a coordinated effect. Interestingly, the decrease of miR-96and miR-185coincided with the increase of SR-BI in the livers of ApoE KO mice on a high-fat diet. These data suggest that miR-185, miR-96, and miR-223may repress selective HDL-C uptake through the inhibition of SR-BI in human hepatic cells, implying a novel mode of regulation of hepatic SR-BI and an important role of microRNAs in modulating cholesterol metabolism.
In the second part of this study, we discovered that several compounds increased SR-BI mRNA stability and confirmed they are regulators of SR-BI expression and function. To facilitate screening of compounds that increased SR-BI mRNA stability in a3'-untranslated region (3'UTR) relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an LUC-3'UTR fusion construct, in which firefly luciferase reporter mRNAs containing the SR-BI3'UTR (LUC-3'UTR). The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. The chemical library containing over25000compounds was screened and analyzed. Compound hits identified by HTS were further evaluated. The effects on SR-BI expression and function were measured in HepG2cells. Six compounds were confirmed to significantly increase SR-BI expression and DiI-HDL uptake. The positive rate of HTS was0.23%o. Treatment with the compound5172B-41or compound5238B-63significantly increased SR-BI mRNA stability, since they lengthened SR-BI mRNA half-life and increased SR-BI mRNA and protein levels. Further studies showed that treatment with both compound5172B-41and compound5238B-63significantly increased expression of SR-BI expression and DiI-HDL uptake in human HepG2cells in a concentration and time dependent manner. To obtain better candidate compounds for future studies, structure-activity relationship analysis was performed. Our hit compounds could be ideal starting points for the development of new drug candidates or lead compounds to treat cardiovascular diseases.
在本研究的第一部分,我们考察了参与肝脏SR-BI基因转录后调控和高密度脂蛋白胆固醇选择性摄取调节机制的microRNA。肝细胞HepG2中,miR-185、 miR-96和miR-223能显著抑制SR-BI表达,并且分别以31.9%(P<0.001)、23.9%(P<0.05)和15.4%(P<0.05)的比例降低DiI-HDL摄取。它们的反义寡核苷酸抑制剂呈现相反的效应。作用位点缺失后,miR-96, miR-185和miR-223失去调节功能,这进一步确证了它们对SR-BI的调节作用。此外,这几个microRNA还能以协同效应的方式直接作用于SR-BI基因mRNA3'UTR序列。更值得关注的是,高脂饲料喂养的ApoE基因敲除小鼠miR-96和miR-185与SR-BI的表达呈截然相反的变化,SR-BI表达增加,而miR-96和miR-185的表达水平降低。这些实验数据表明,人类肝细胞中,miR-185、miR-96和miR-223可以通过抑制SR-BI的表达来抑制HDL-C选择性摄取。这一发现是肝脏SR-BI基因表达调控的新模式,同时也揭示了microRNA参与胆固醇代谢调节的新机制。
在本研究的第二部分,我们发现和确证了几个具有增强SR-BI基因mRNA稳定性功能的小分子化合物,并明确了它们调节SR-BI表达和功能的作用。我们将人SR-BI基因mRNA3'UTR序列构建在荧光素酶报告基因下游,建立以稳定转染HepG2细胞为基础的高通量筛选模型,筛选3'UTR序列相关的能够显著增强SR-BI基因mRNA稳定性的小分子化合物。筛选条件的优化和模型参数的评价表明该模型符合高通量筛选的要求,合理有效,可用于微生物次级代谢产物库和化合物库的大规模高通量筛选。通过对国家新药(微生物)筛选中心化合物库提供的25755个化合物的多轮筛选,获得6个阳性化合物,筛选阳性率0.23‰。获得的六个阳性化合物均能有效提高肝细胞SR-BI表达和DiI-HDL选择性摄取。进一步研究表明,化合物5172B-41和5238B-63能够有效延长肝细胞SR-BI基因mRNA半衰期,提高SR-BI基因mRNA水平和蛋白表达水平,从而明确了它们增强肝细胞SR-BI基因mRNA稳定性的功能。化合物5172B-41和5238B-63以时间依赖性和剂量依赖性的方式影响SR-BI基因表达和肝细胞对DiI-HDL的选择性摄取。构效关系分析为进一步获得更好活性的候选化合物提供了很多有益参考。本研究获得的阳性小分子化合物具有明确的作用靶点,有可能发展成为新型心血管疾病治疗候选药物或先导化合物,并有助于对SR-BI基因转录后调控机制进行深入研究。
Despite significant improvements in the cardiovascular health in recent decades, cardiovascular disease (CVD) continues to be the leading cause of morbidity and mortality worldwide. It imposes a significant burden in terms of costs, premature death, long-term disability, restricted social functioning and reduction in patient's quality of life. Effective interventions in cardiovascular disease treatment and prevention have long-term clinical and economic consequences. Since atherosclerosis is the central biological process underlying most cardiovascular diseases, new and better anti-atherosclerotic strategies are required. Plasma concentrations of high density lipoprotein (HDL) have been known to inversely correlate with risk for atherosclerosis. Bulk transport of HDL cholesterol from the peripheral tissues to the liver is a major pathway, termed reverse cholesterol transport, responsible for maintaining whole body cholesterol homeostasis. A key mechanism of receptor-mediated direct delivery of HDL cholesteryl esters to the liver and steroidogenic tissues is selective cholesterol uptake. Scavenger receptor class B type I (SR-BI), HDL receptor, mediates the selective uptake of plasma HDL cholesterol by the liver and steroidogenic tissues. Increasing the expression of hepatic SR-BI promotes reverse cholesterol transport and reduces atherosclerosis. Therefore, SR-BI has considerable antiatherogenic capacity. SR-BI may become an attractive target for prevention of or therapeutic intervention in a variety of human diseases.
In the first part of this study, the potential involvement of microRNAs in posttranscriptional regulation of hepatic SR-BI and selective HDL-C uptake was investigated. The level of SR-BI expression was repressed by miR-185, miR-96, and miR-223, while the uptake of DiI-HDL was decreased by31.9%(P<0.001),23.9%(P <0.05), and15.4%(P<0.05), respectively, in HepG2cells. The inhibition of these microRNAs by their anti-microRNAs had opposite effects in these hepatic cells. The critical effect of miR-185was further validated by the loss of regulation in constructs with mutated miR-96, miR-185and miR-223target sites. In addition, these microRNAs directly targeted the3'untranslated region (UTR) of SR-BI with a coordinated effect. Interestingly, the decrease of miR-96and miR-185coincided with the increase of SR-BI in the livers of ApoE KO mice on a high-fat diet. These data suggest that miR-185, miR-96, and miR-223may repress selective HDL-C uptake through the inhibition of SR-BI in human hepatic cells, implying a novel mode of regulation of hepatic SR-BI and an important role of microRNAs in modulating cholesterol metabolism.
In the second part of this study, we discovered that several compounds increased SR-BI mRNA stability and confirmed they are regulators of SR-BI expression and function. To facilitate screening of compounds that increased SR-BI mRNA stability in a3'-untranslated region (3'UTR) relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an LUC-3'UTR fusion construct, in which firefly luciferase reporter mRNAs containing the SR-BI3'UTR (LUC-3'UTR). The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. The chemical library containing over25000compounds was screened and analyzed. Compound hits identified by HTS were further evaluated. The effects on SR-BI expression and function were measured in HepG2cells. Six compounds were confirmed to significantly increase SR-BI expression and DiI-HDL uptake. The positive rate of HTS was0.23%o. Treatment with the compound5172B-41or compound5238B-63significantly increased SR-BI mRNA stability, since they lengthened SR-BI mRNA half-life and increased SR-BI mRNA and protein levels. Further studies showed that treatment with both compound5172B-41and compound5238B-63significantly increased expression of SR-BI expression and DiI-HDL uptake in human HepG2cells in a concentration and time dependent manner. To obtain better candidate compounds for future studies, structure-activity relationship analysis was performed. Our hit compounds could be ideal starting points for the development of new drug candidates or lead compounds to treat cardiovascular diseases.
引文
[1]McClelland RL, Nasir K, Budoff M, et al. Arterial age as a function of coronary artery calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]) [J]. The American journal of cardiology,2009,103(1):59-63.
[2]Stein JH. Carotid intima-media thickness and vascular age:you are only as old as your arteries look [J]. Journal of the American Society of Echocardiography. official publication of the American Society of Echocardiography,2004,17(6):686-9.
[3]Bliss M. William Osler:a life in medicine [M]. Oxford University Press, 1999.
[4]世界卫生组织.2010年全球非传染性疾病现状报告,2011,日内瓦.
[5]卫生部心血管病防治研究中心.中国心血管病报告2011[M].中国大 百科全书出版社,2012.8.10.
[6]Alkerwi A, Guillaume M, Zannad F, et al. Nutrition, environment and cardiovascular health (NESCAV):protocol of an inter-regional cross-sectional study [J]. BMC public health,2010,10:698.
[7]世界卫生组织.心血管疾病预防心血管风险评估和管理袖珍指南[M].日内瓦,2008.
[8]Jashari F, Ibrahimi P, Nicoll R, et al. Coronary and carotid atherosclerosis: Similarities and differences [J]. Atherosclerosis,2013,227(2):193-200.
[9]Cohen Tervaert JW. Cardiovascular disease due to accelerated atherosclerosis in systemic vasculitides [J]. Best practice & research Clinical rheumatology,2013,27(1):33-44.
[10]Ference BA, Yoo W, Alesh I, et al. Effect of Long-Term Exposure to Lower Low-Density Lipoprotein Cholesterol Beginning Early in Life on the Risk of Coronary Heart Disease:A Mendelian Randomization Analysis [J]. Journal of the American College of Cardiology,2012,
[11]Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol:a meta-analysis of data from 170,000 participants in 26 randomised trials [J]. Lancet,2010,376(9753):1670-81.
[12]Goldstein JL, Brown MS. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia [J]. The Journal of biological chemistry,1974,249(16):5153-62.
[13]Musunuru K. Atherogenic dyslipidemia:cardiovascular risk and dietary intervention [J]. Lipids,2010,45(10):907-14.
[14]Weissglas-Volkov D, Pajukanta P. Genetic causes of high and low serum HDL-cholesterol [J]. Journal of lipid research,2010,51(8):2032-57.
[15]Rosenson RS, Brewer HB, Jr., Davidson WS, et al. Cholesterol efflux and atheroprotection:advancing the concept of reverse cholesterol transport [J]. Circulation,2012,125(15):1905-19.
[16]Badimon L, Vilahur G. LDL-cholesterol versus HDL-cholesterol in the atherosclerotic plaque:inflammatory resolution versus thrombotic chaos [J]. Annals of the New York Academy of Sciences,2012,1254:18-32.
[17]Mureddu GF, Brandimarte F, De Luca L. High-density lipoprotein levels and risk of cardiovascular events:a review [J]. J Cardiovasc Med (Hagerstown),2012, 13(9):575-86.
[18]Singh V, Sharma R, Kumar A, et al. Low high-density lipoprotein cholesterol:current status and future strategies for management [J]. Vascular health and risk management,2010,6:979-96.
[19]Tomkin GH. Atherosclerosis, diabetes and lipoproteins [J]. Expert review of cardiovascular therapy,2010,8(7):1015-29.
[20]Glomset JA. The metabolic role of lecithin:cholesterol acyltransferase: perspectives from pathology [J]. Advances in lipid research,1973,11(0):1-65.
[21]Brufau G, Groen AK, Kuipers F. Reverse cholesterol transport revisited: contribution of biliary versus intestinal cholesterol excretion [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2011,31(8):1726-33.
[22]Berrougui H, Khalil A. Age-associated decrease of high-density lipoprotein-mediated reverse cholesterol transport activity [J]. Rejuvenation research, 2009,12(2):117-26.
[23]Berrougui H, Momo CN, Khalil A. Health benefits of high-density lipoproteins in preventing cardiovascular diseases [J]. Journal of clinical lipidology, 2012,6(6):524-33.
[24]Fisher EA, Feig JE, Hewing B, et al. High-density lipoprotein function, dysfunction, and reverse cholesterol transport [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2012,32(12):2813-20.
[25]Eren E, Yilmaz N, Aydin O. High Density Lipoprotein and it's Dysfunction [J]. The open biochemistry journal,2012,6:78-93.
[26]Mackness B, Mackness M. The antioxidant properties of high-density lipoproteins in atherosclerosis [J]. Panminerva medica,2012,54(2):83-90.
[27]Boden WE. High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease:assessing the data from Framingham to the Veterans Affairs High--Density Lipoprotein Intervention Trial [J]. The American journal of cardiology,2000,86(12A):19L-22L.
[28]Barter P. HDL-C:role as a risk modifier [J]. Atherosclerosis Supplements, 2011,12(3):267-70.
[29]Lee JM, Choudhury RP. Atherosclerosis regression and high-density lipoproteins [J]. Expert review of cardiovascular therapy,2010,8(9):1325-34.
[30]Alwaili K, Awan Z, Alshahrani A, et al. High-density lipoproteins and cardiovascular disease:2010 update [J]. Expert review of cardiovascular therapy,2010, 8(3):413-23.
[31]Kapur NK, Ashen D, Blumenthal RS. High density lipoprotein cholesterol: an evolving target of therapy in the management of cardiovascular disease [J]. Vascular health and risk management,2008,4(1):39-57.
[32]Acton S, Rigotti A, Landschulz KT, et al. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor [J]. Science,1996,271(5248): 518-20.
[33]Rigotti A, Miettinen HE, Krieger M. The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues [J]. Endocrine reviews,2003,24(3):357-87.
[34]Saddar S, Mineo C, Shaul PW. Signaling by the high-affinity HDL receptor scavenger receptor B type I [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2010,30(2):144-50.
[35]Kocher O, Krieger M. Role of the adaptor protein PDZK1 in controlling the HDL receptor SR-BI [J]. Current opinion in lipidology,2009,20(3):236-41.
[36]Webb NR, de Villiers WJ, Connell PM, et al. Alternative forms of the scavenger receptor BI (SR-BI) [J]. Journal of lipid research,1997,38(7):1490-5.
[37]Glass C, Pittman RC, Weinstein DB, et al. Dissociation of tissue uptake of cholesterol ester from that of apoprotein A-I of rat plasma high density lipoprotein: selective delivery of cholesterol ester to liver, adrenal, and gonad [J]. Proceedings of the National Academy of Sciences of the United States of America,1983,80(17): 5435-9.
[38]Glass C, Pittman RC, Civen M, et al. Uptake of high-density lipoprotein-associated apoprotein A-I and cholesterol esters by 16 tissues of the rat in vivo and by adrenal cells and hepatocytes in vitro [J]. The Journal of biological chemistry,1985,260(2):744-50.
[39]Arai T, Wang N, Bezouevski M, et al. Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene [J]. The Journal of biological chemistry,1999,274(4):2366-71.
[40]Kozarsky KF, Donahee MH, Glick JM, et al. Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2000,20(3):721-7.
[41]Ueda Y, Gong E, Royer L, et al. Relationship between expression levels and atherogenesis in scavenger receptor class B, type I transgenics [J]. The Journal of biological chemistry,2000,275(27):20368-73.
[42]Zhang Y, Da Silva JR, Reilly M, et al. Hepatic expression of scavenger receptor class B type I (SR-BI) is a positive regulator of macrophage reverse cholesterol transport in vivo [J]. The Journal of clinical investigation,2005,115(10): 2870-4.
[43]Rader DJ, Alexander ET, Weibel GL, et al. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis [J]. Journal of lipid research,2009,50 Suppl:S189-94.
[44]Trigatti B, Rayburn H, Vinals M, et al. Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology [J]. Proceedings of the National Academy of Sciences of the United States of America, 1999,96(16):9322-7.
[45]Matoulkova E, Michalova E, Vojtesek B, et al. The role of the 3' untranslated region in post-transcriptional regulation of protein expression in mammalian cells [J]. RNA biology,2012,9(5):563-76.
[46]Bava FA, Eliscovich C, Ferreira PG, et al. CPEB1 coordinates alternative 3'-UTR formation with translational regulation [J]. Nature,2013,495(7439):121-5.
[47]Hoshino S. Mechanism of the initiation of mRNA decay:role of eRF3 family G proteins [J]. Wiley interdisciplinary reviews RNA,2012,3(6):743-57.
[48]Pichon X, Wilson LA, Stoneley M, et al. RNA binding protein/RNA element interactions and the control of translation [J]. Current protein & peptide science,2012,13(4):294-304.
[49]Adeli K. Translational control mechanisms in metabolic regulation: critical role of RNA binding proteins, microRNAs, and cytoplasmic RNA granules [J]. American journal of physiology Endocrinology and metabolism,2011,301(6): E1051-64.
[50]Barrett LW, Fletcher S, Wilton SD. Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements [J]. Cellular and molecular life sciences:CMLS,2012,69(21):3613-34.
[51]Chen W, Wang S, Ma Y, et al. Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response [J]. International journal of molecular medicine,2008,21(3): 345-53.
[52]Kong W, Wei J, Abidi P, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins [J]. Nature medicine, 2004,10(12):1344-51.
[53]Abidi P, Zhou Y, Jiang JD, et al. Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine [J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2005,25(10):2170-6.
[54]Lee S, Vasudevan S. Post-transcriptional stimulation of gene expression by microRNAs [J]. Advances in experimental medicine and biology,2013,768: 97-126.
[55]Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and function [J]. Thrombosis and haemostasis,2012,107(4):605-10.
[56]Mo YY. MicroRNA regulatory networks and human disease [J]. Cellular and molecular life sciences:CMLS,2012,69(21):3529-31.
[57]Iatan I, Palmyre A, Alrasheed S, et al. Genetics of cholesterol efflux [J]. Current atherosclerosis reports,2012,14(3):235-46.
[58]Sakurai F, Katayama K, Mizuguchi H. MicroRNA-regulated transgene expression systems for gene therapy and virotherapy [J]. Frontiers in bioscience:a journal and virtual library,2011,16:2389-401.
[l]司徒镇强,吴军正.细胞培养[M].世界图书出版公司,2007.
[2]Heckman KL, Pease LR. Gene splicing and mutagenesis by PCR-driven overlap extension [J]. Nature protocols,2007,2(4):924-32.
[3]Carl W. Dieffenbach GSD著,俞炜源,陈添弥译.PCR技术实验指南PCR Primer:A Laboratory Manual [M].第二版.科学出版社,2003.
[4]Frederick M. Ausubel RB, Robert E. Kingston, David D. Moore, J. G. Seidman, John A. Smith, Kevin Struhl,著,颜子颖王海林译.精编分子生物学实验指南Short Protocols in Molecular Biology [M].第五版：科学出版社,2008.
[5]John J. Sambrook DWR著.分子克隆实验指南Molecular Cloning:A Laboratory Manual [M].第三版：科学出版社,2002.
[6]Gu X, Lawrence R, Krieger M. Dissociation of the high density lipoprotein and low density lipoprotein binding activities of murine scavenger receptor class B type I (mSR-BI) using retrovirus library-based activity dissection [J]. The Journal of biological chemistry,2000,275(13):9120-30.
[7]Jurgens G, Xu QB, Huber LA, et al. Promotion of lymphocyte growth by high density lipoproteins (HDL). Physiological significance of the HDL binding site [J]. The Journal of biological chemistry,1989,264(15):8549-56.
[8]Traill KN, Jurgens G, Bock G, et al. High density lipoprotein uptake by freshly isolated human peripheral blood T lymphocytes [J]. Immunobiology,1987, 175(5):447-54.
[9]Xu Q, Buhler E, Steinmetz A, et al. A high-density-lipoprotein receptor appears to mediate the transfer of essential fatty acids from high-density lipoprotein to lymphocytes [J]. The Biochemical journal,1992,287 (Pt 2):395-401.
[10]Habelhah H, Frew IJ, Laine A, et al. Stress-induced decrease in TRAF2 stability is mediated by Siah2 [J]. The EMBO journal,2002,21(21):5756-65.
[11]Hughes R, Gilley J, Kristiansen M, et al. The MEK-ERK pathway negatively regulates bim expression through the 3'UTR in sympathetic neurons [J]. BMC neuroscience,2011,12:69.
[12]Shock JL, Fischer KF, DeRisi JL. Whole-genome analysis of mRNA decay in Plasmodium falciparum reveals a global lengthening of mRNA half-life during the intra-erythrocytic development cycle [J]. Genome biology,2007,8(7): R134.
[13]Wang Y, Hacker A, Murray-Stewart T, et al. Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein [J]. The Biochemical journal,2005,386(Pt 3):543-7.
[14]Chen C, Liang W, Jia J, et al. Aldosterone induces apoptosis in rat podocytes:role of PI3-K/Akt and p38MAPK signaling pathways [J]. Nephron Experimental nephrology,2009,113(1):e26-34.
[15]Chen S, Cheng AC, Wang MS, et al. Detection of apoptosis induced by new type gosling viral enteritis virus in vitro through fluorescein annexin V-FITC/PI double labeling [J]. World journal of gastroenterology:WJG,2008,14(14):2174-8.
[16]Kang X, Xie Q, Zhou X, et al. Effects of hepatitis B virus S protein exposure on sperm membrane integrity and functions [J]. PloS one,2012,7(3): e33471.
[17]Mattes MJ. Apoptosis assays with lymphoma cell lines:problems and pitfalls [J]. British journal of cancer,2007,96(6):928-36.
[1]Guttilla IK, White BA. Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells [J]. The Journal of biological chemistry, 2009,284(35):23204-16.
[2]Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis [J]. Nature,2005, 436(7048):214-20.
[3]Long D, Lee R, Williams P, et al. Potent effect of target structure on microRNA function [J]. Nature structural & molecular biology,2007,14(4):287-94.
[4]Matzura O, Wennborg A. RNAdraw:an integrated program for RNA secondary structure calculation and analysis under 32-bit Microsoft Windows [J]. Computer applications in the biosciences:CABIOS,1996,12(3):247-9.
[5]Reuter JS, Mathews DH. RNAstructure:software for RNA secondary structure prediction and analysis [J]. BMC bioinformatics,2010,11:129.
[6]Betel D, Koppal A, Agius P, et al. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites [J]. Genome biology,2010,11(8):R90.
[7]Betel D, Wilson M, Gabow A, et al. The microRNA.org resource:targets and expression [J]. Nucleic acids research,2008,36(Database issue):D149-53.
[8]John B, Enright AJ, Aravin A, et al. Human MicroRNA targets [J]. PLoS biology,2004,2(11):e363.
[9]Hu Z, Shen WJ, Kraemer FB, et al. MicroRNAs 125a and 455 repress lipoprotein-supported steroidogenesis by targeting scavenger receptor class B type I in steroidogenic cells [J]. Molecular and cellular biology,2012,32(24):5035-45.
[10]Larkin MA, Blackshields G, Brown NP, et al. Clustal W and Clustal X version 2.0 [J]. Bioinformatics,2007,23(21):2947-8.
[11]Crooks GE, Hon G, Chandonia JM, et al. WebLogo:a sequence logo generator [J]. Genome research,2004,14(6):1188-90.
[12]Chinetti G, Gbaguidi FG, Griglio S, et al. CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors [J]. Circulation,2000,101(20):2411-7.
[13]Tiwari RL, Singh V, Barthwal MK. Macrophages:an elusive yet emerging therapeutic target of atherosclerosis [J]. Medicinal research reviews,2008, 28(4):483-544.
[14]Covey SD, Krieger M, Wang W, et al. Scavenger receptor class B type I-mediated protection against atherosclerosis in LDL receptor-negative mice involves its expression in bone marrow-derived cells [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2003,23(9):1589-94.
[15]Zhao GJ, Yin K, Fu YC, et al. The interaction of ApoA-I and ABCA1 triggers signal transduction pathways to mediate efflux of cellular lipids [J]. Mol Med, 2012,18:149-58.
[16]Iatan I, Palmyre A, Alrasheed S, et al. Genetics of cholesterol efflux [J]. Current atherosclerosis reports,2012,14(3):235-46.
[17]Liu Y, Tang C. Regulation of ABCA1 functions by signaling pathways [J]. Biochimica et biophysica acta,2012,1821(3):522-9.
[18]Buechler C, Bauer S. ATP binding cassette transporter A1 (ABCA1) associated proteins:potential drug targets in the metabolic syndrome and atherosclerotic disease? [J]. Current pharmaceutical biotechnology,2012,13(2): 319-30.
[19]Charlton-Menys V, Durrington PN. Human cholesterol metabolism and therapeutic molecules [J]. Experimental physiology,2008,93(1):27-42.
[20]Yao RE, Wang J, Geng J, et al. Identification of LDLR mutations in two Chinese pedigrees with familial hypercholesterolemia [J]. Journal of pediatric endocrinology & metabolism:JPEM,2012,25(7-8):769-73.
[21]Skalen K, Gustafsson M, Rydberg EK, et al. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis [J]. Nature,2002,417(6890):750-4.
[22]Sorrentino V, Zelcer N. Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor [J]. Current opinion in lipidology,2012,23(3):213-9.
[23]Dekkers JF, van der Ent CK, Kalkhoven E, et al. PPARgamma as a therapeutic target in cystic fibrosis [J]. Trends in molecular medicine,2012,18(5): 283-91.
[24]Floyd ZE, Stephens JM. Controlling a master switch of adipocyte development and insulin sensitivity:covalent modifications of PPARgamma [J]. Biochimica et biophysica acta,2012,1822(7):1090-5.
[25]Abbas A, Blandon J, Rude J, et al. PPAR-gamma agonist in treatment of diabetes:cardiovascular safety considerations [J]. Cardiovascular & hematological agents in medicinal chemistry,2012,10(2):124-34.
[26]Lamers C, Schubert-Zsilavecz M, Merk D. Therapeutic modulators of peroxisome proliferator-activated receptors (PPAR):a patent review (2008-present) [J]. Expert opinion on therapeutic patents,2012,22(7):803-41.
[27]Cariou B, Charbonnel B, Staels B. Thiazolidinediones and PPARgamma agonists:time for a reassessment [J]. Trends in endocrinology and metabolism:TEM, 2012,23(5):205-15.
[28]Agrawal R, Jain P, Dikshit SN. Balaglitazone:a second generation peroxisome proliferator-activated receptor (PPAR) gamma (gamma) agonist [J]. Mini reviews in medicinal chemistry,2012,12(2):87-97.
[29]Huang JV, Greyson CR, Schwartz GG. PPAR-gamma as a therapeutic target in cardiovascular disease:evidence and uncertainty [J]. Journal of lipid research, 2012,53(9):1738-54.
[30]Ciudin A, Hernandez C, Simo R. Update on cardiovascular safety of PPARgamma agonists and relevance to medicinal chemistry and clinical pharmacology [J]. Current topics in medicinal chemistry,2012,12(6):585-604.
[31]Balakumar P, Kathuria S. Submaximal PPARgamma activation and endothelial dysfunction:new perspectives for the management of cardiovascular disorders [J]. British journal of pharmacology,2012,166(7):1981-92.
[32]Rottiers V, Naar AM. MicroRNAs in metabolism and metabolic disorders [J]. Nature reviews Molecular cell biology,2012,13(4):239-50.
[33]Rottiers V, Najafi-Shoushtari SH, Kristo F, et al. MicroRNAs in metabolism and metabolic diseases [J]. Cold Spring Harbor symposia on quantitative biology,2011,76:225-33.
[34]Ambros V. The functions of animal microRNAs [J]. Nature,2004, 431(7006):350-5.
[35]Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease [J]. Circulation,2010,121(8):1022-32.
[36]Suarez Y, Sessa WC. MicroRNAs as novel regulators of angiogenesis [J]. Circulation research,2009,104(4):442-54.
[37]Perera RJ, Ray A. MicroRNAs in the search for understanding human diseases [J]. BioDrugs:clinical immunotherapeutics, biopharmaceuticals and gene therapy,2007,21(2):97-104.
[38]O'Neill LA, Sheedy FJ, McCoy CE. MicroRNAs:the fine-tuners of Toll-like receptor signalling [J]. Nature reviews Immunology,2011,11(3):163-75.
[39]Ha TY. MicroRNAs in Human Diseases:From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases [J]. Immune network,2011,11(5): 227-44.
[40]Ha TY. MicroRNAs in Human Diseases:From Cancer to Cardiovascular Disease [J]. Immune network,2011,11(3):135-54.
[41]Pallante P, Visone R, Croce CM, et al. Deregulation of microRNA expression in follicular-cell-derived human thyroid carcinomas [J]. Endocrine-related cancer,2010,17(1):F91-104.
[42]Belver L, de Yebenes VG, Ramiro AR. MicroRNAs prevent the generation of autoreactive antibodies [J]. Immunity,2010,33(5):713-22.
[43]Najafi-Shoushtari SH. MicroRNAs in cardiometabolic disease [J]. Current atherosclerosis reports,2011,13(3):202-7.
[44]Fernandez-Hernando C, Suarez Y, Rayner KJ, et al. MicroRNAs in lipid metabolism [J]. Current opinion in lipidology,2011,22(2):86-92.
[45]Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting [J]. Cell metabolism,2006,3(2): 87-98.
[46]Najafi-Shoushtari SH, Kristo F, Li Y, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis [J]. Science,2010,328(5985): 1566-9.
[47]Rayner KJ, Suarez Y, Davalos A, et al. MiR-33 contributes to the regulation of cholesterol homeostasis [J]. Science,2010,328(5985):1570-3.
[48]Ramirez CM, Davalos A, Goedeke L, et al. MicroRNA-758 regulates cholesterol efflux through posttranscriptional repression of ATP-binding cassette transporter A1 [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2011,31(11): 2707-14.
[49]Vickers KC, Palmisano BT, Shoucri BM, et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins [J]. Nature cell biology,2011,13(4):423-33.
[50]Trigatti BL, Krieger M, Rigotti A. Influence of the HDL receptor SR-BI on lipoprotein metabolism and atherosclerosis [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2003,23(10):1732-8.
[51]Zhang X, Moor AN, Merkler KA, et al. Regulation of alternative splicing of liver scavenger receptor class B gene by estrogen and the involved regulatory splicing factors [J]. Endocrinology,2007,148(11):5295-304.
[52]Leiva A, Verdejo H, Benitez ML, et al. Mechanisms regulating hepatic SR-BI expression and their impact on HDL metabolism [J]. Atherosclerosis,2011, 217(2):299-307.
[53]Hirano K, Ikegami C, Tsujii K, et al. Probucol enhances the expression of human hepatic scavenger receptor class B type I, possibly through a species-specific mechanism [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2005,25(11): 2422-7.
[54]Shetty S, Eckhardt ER, Post SR, et al. Phosphatidylinositol-3-kinase regulates scavenger receptor class B type I subcellular localization and selective lipid uptake in hepatocytes [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2006, 26(9):2125-31.
[55]Krek A, Grun D, Poy MN, et al. Combinatorial microRNA target predictions [J]. Nature genetics,2005,37(5):495-500.
[56]Thomas M, Lieberman J, Lal A. Desperately seeking microRNA targets [J]. Nature structural & molecular biology,2010,17(10):1169-74.
[57]Yesilaltay A, Daniels K, Pal R, et al. Loss of PDZK1 causes coronary artery occlusion and myocardial infarction in Paigen diet-fed apolipoprotein E deficient mice [J]. PloS one,2009,4(12):e8103.
[58]Huby T, Doucet C, Dachet C, et al. Knockdown expression and hepatic deficiency reveal an atheroprotective role for SR-BI in liver and peripheral tissues [J]. The Journal of clinical investigation,2006,116(10):2767-76.
[59]Ji A, Meyer JM, Cai L, et al. Scavenger receptor SR-BI in macrophage lipid metabolism [J]. Atherosclerosis,2011,217(1):106-12.
[60]Yvan-Charvet L, Wang N, Tall AR. Role of HDL, ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses [J]. Arteriosclerosis, thrombosis, and vascular biology,2010,30(2):139-43.
[61]Zhang Z, Tang H, Wang Z, et al. MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma [J]. Molecular cancer,2011,10(124.
[62]Liu M, Lang N, Chen X, et al. miR-185 targets RhoA and Cdc42 expression and inhibits the proliferation potential of human colorectal cells [J]. Cancer letters,2011,301(2):151-60.
[63]Kuhn S, Johnson SL, Furness DN, et al. miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells [J]. Proceedings of the National Academy of Sciences of the United States of America,2011,108(6): 2355-60.
[64]Johnnidis JB, Harris MH, Wheeler RT, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223 [J]. Nature,2008,451(7182): 1125-9.
[65]Zhuang G, Meng C, Guo X, et al. A novel regulator of macrophage activation:miR-223 in obesity-associated adipose tissue inflammation [J]. Circulation, 2012,125(23):2892-903.
[66]Xu XM, Qian JC, Deng ZL, et al. Expression of miR-21, miR-31, miR-96 and miR-135b is correlated with the clinical parameters of colorectal cancer [J]. Oncology letters,2012,4(2):339-45.
[67]Lin H, Dai T, Xiong H, et al. Unregulated miR-96 induces cell proliferation in human breast cancer by downregulating transcriptional factor FOXO3a [J]. PloS one,2010,5(12):e15797.
[68]Li J, Guo Y, Liang X, et al. MicroRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4 [J]. Journal of cancer research and clinical oncology,2012,138(5):763-74.
[69]Zeng X, Xiang J, Wu M, et al. Circulating miR-17, miR-20a, miR-29c, and miR-223 combined as non-invasive biomarkers in nasopharyngeal carcinoma [J]. PloS one,2012,7(10):e46367.
[70]Ebert KM, Paynton BV, McKnight GS, et al. Translation and stability of ovalbumin messenger RNA injected into growing oocytes and fertilized ova of mice [J]. Journal of embryology and experimental morphology,1984,84:91-103.
[71]Leys EJ, Crouse GF, Kellems RE. Dihydrofolate reductase gene expression in cultured mouse cells is regulated by transcript stabilization in the nucleus [J]. The Journal of cell biology,1984,99(1 Pt 1):180-7.
[72]Dani C, Mechti N, Piechaczyk M, et al. Increased rate of degradation of c-myc mRNA in interferon-treated Daudi cells [J]. Proceedings of the National Academy of Sciences of the United States of America,1985,82(15):4896-9.
[73]Kislauskis EH, Li Z, Singer RH, et al. Isoform-specific 3'-untranslated sequences sort alpha-cardiac and beta-cytoplasmic actin messenger RNAs to different cytoplasmic compartments [J]. The Journal of cell biology,1993,123(1):165-72.
[74]Kislauskis EH, Zhu X, Singer RH. Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype [J]. The Journal of cell biology,1994,127(2):441-51.
[75]Suay L, Salvador ML, Abesha E, et al. Specific roles of 5'RNA secondary structures in stabilizing transcripts in chloroplasts [J]. Nucleic acids research,2005,33(15):4754-61.
[76]Ross J. Control of messenger RNA stability in higher eukaryotes [J]. Trends in genetics:TIG,1996,12(5):171-5.
[77]Gutierrez RA, Macintosh GC, Green PJ. Current perspectives on mRNA stability in plants:multiple levels and mechanisms of control [J]. Trends in plant science,1999,4(11):429-38.
[78]Mitchell P, Tollervey D. mRNA turnover [J]. Current opinion in cell biology,2001,13(3):320-5.
[79]Huang HW, Payne DE, Bi W, et al. Sequences of a hairpin structure in the 3'-untranslated region mediate regulation of human pulmonary surfactant protein B mRNA stability [J]. American journal of physiology Lung cellular and molecular physiology,2012,302(10):L1107-17.
[80]Anant S, Davidson NO. An AU-rich sequence element (UUUN[A/U]U) downstream of the edited C in apolipoprotein B mRNA is a high-affinity binding site for Apobec-1:binding of Apobec-1 to this motif in the 3'untranslated region of c-myc increases mRNA stability [J]. Molecular and cellular biology,2000,20(6):1982-92.
[81]Paschoud S, Dogar AM, Kuntz C, et al. Destabilization of interleukin-6 mRNA requires a putative RNA stem-loop structure, an AU-rich element, and the RNA-binding protein AUF1 [J]. Molecular and cellular biology,2006,26(22): 8228-41.
[82]Guhaniyogi J, Brewer G. Regulation of mRNA stability in mammalian cells [J]. Gene,2001,265(1-2):11-23.
[83]Gaspar P, Moura G, Santos MA, et al. mRNA secondary structure optimization using a correlated stem-loop prediction [J]. Nucleic acids research,2013, 41(6):e73.
[84]Bolukbasi MF, Mizrak A, Ozdener GB, et al. miR-1289 and "Zipcode"-like Sequence Enrich mRNAs in Microvesicles [J]. Molecular therapy Nucleic acids,2012,1:e 10.
[85]Zhang M, Lam TT, Tonelli M, et al. Interaction of the histone mRNA hairpin with stem-loop binding protein (SLBP) and regulation of the SLBP-RNA complex by phosphorylation and proline isomerization [J]. Biochemistry,2012,51(15): 3215-31.
[86]Tan D, Marzluff WF, Dominski Z, et al. Structure of histone mRNA stem-loop, human stem-loop binding protein, and 3'hExo ternary complex [J]. Science, 2013,339(6117):318-21.
[1]Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 [J]. Cell,1993, 75(5):843-54.
[2]Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans [3]. Cell,1993,75(5):855-62.
[3]Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans [J]. Nature,2000, 403(6772):901-6.
[4]Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets [J]. Cell, 2005,120(1):15-20.
[5]Sandhu SK, Croce CM, Garzon R. Micro-RNA Expression and Function in Lymphomas [J]. Advances in hematology,2011,2011:347137.
[6]Ambros V. The functions of animal microRNAs [J]. Nature,2004, 431(7006):350-5.
[7]Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function [J].Cell,2004,116(2):281-97.
[8]Cordes KR, Srivastava D, Ivey KN. MicroRNAs in cardiac development [J]. Pediatric cardiology,2010,31(3):349-56.
[9]Lagos-Quintana M, Rauhut R, Lendeckel W, et al. Identification of novel genes coding for small expressed RNAs [J]. Science,2001,294(5543):853-8.
[10]Lau NC, Lim LP, Weinstein EG, et al. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans [J]. Science,2001,294(5543): 858-62.
[11]Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans [J]. Science,2001,294(5543):862-4.
[12]Ambros V, Bartel B, Bartel DP, et al. A uniform system for microRNA annotation [J]. RNA,2003,9(3):277-9.
[13]Griffiths-Jones S, Grocock RJ, van Dongen S, et al. miRBase:microRNA sequences, targets and gene nomenclature [J]. Nucleic acids research,2006, 34(Database issue):D140-4.
[14]Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology [J]. Nature,2011,469(7330):336-42.
[15]Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease [J]. Circulation,2010,121(8):1022-32.
[16]Ji R, Cheng Y, Yue J, et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation [J]. Circulation research,2007,100(11):1579-88.
[17]Elia L, Quintavalle M, Zhang J, et al. The knockout of miR-143 and-145 alters smooth muscle cell maintenance and vascular homeostasis in mice:correlates with human disease [J]. Cell death and differentiation,2009,16(12):1590-8.
[18]Cheng Y, Liu X, Yang J, et al. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation [J]. Circulation research,2009,105(2):158-66.
[19]Xu S, Jin C, Shen X, et al. MicroRNAs as potential novel therapeutic targets and tools for regulating paracrine function of endothelial progenitor cells [J]. Medical science monitor:international medical journal of experimental and clinical research,2012,18(7):HY27-31.
[20]Little PJ, Ballinger ML, Osman N. Vascular wall proteoglycan synthesis and structure as a target for the prevention of atherosclerosis [J]. Vascular health and risk management,2007,3(1):117-24.
[21]Glass CK, Witztum JL. Atherosclerosis. the road ahead [J]. Cell,2001, 104(4):503-16.
[22]Ross R. Atherosclerosis--an inflammatory disease [J]. The New England journal of medicine,1999,340(2):115-26.
[23]Vickers KC, Remaley AT. MicroRNAs in atherosclerosis and lipoprotein metabolism [J]. Current opinion in endocrinology, diabetes, and obesity,2010,17(2): 150-5.
[24]Widlansky ME, Gokce N, Keaney JF, Jr., et al. The clinical implications of endothelial dysfunction [J]. Journal of the American College of Cardiology,2003, 42(7):1149-60.
[25]Endemann DH, Schiffrin EL. Endothelial dysfunction [J]. Journal of the American Society of Nephrology:JASN,2004,15(8):1983-92.
[26]Kuehbacher A, Urbich C, Zeiher AM, et al. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis [J]. Circulation research,2007, 101(1):59-68.
[27]Minami Y, Satoh M, Maesawa C, et al. Effect of atorvastatin on microRNA 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease [J]. European journal of clinical investigation,2009, 39(5):359-67.
[28]Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway [J]. The Journal of clinical investigation,2001,108(3):391-7.
[29]Hulsmans M, De Keyzer D, Holvoet P. MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis [J]. FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 2011,25(8):2515-27.
[30]Lynn FC. Meta-regulation:microRNA regulation of glucose and lipid metabolism [J]. Trends in endocrinology and metabolism:TEM,2009,20(9):452-9.
[31]Dietschy JM, Turley SD. Control of cholesterol turnover in the mouse [J]. The Journal of biological chemistry,2002,277(6):3801-4.
[32]Chen XM. MicroRNA signatures in liver diseases [J]. World journal of gastroenterology:WJG,2009,15(14):1665-72.
[33]Fernandez-Hernando C, Suarez Y, Rayner KJ, et al. MicroRNAs in lipid metabolism [J]. Current opinion in lipidology,2011,22(2):86-92.
[34]Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting [J]. Cell metabolism,2006,3(2): 87-98.
[35]Elmen J, Lindow M, Schutz S, et al. LNA-mediated microRNA silencing in non-human primates [J]. Nature,2008,452(7189):896-9.
[36]Iliopoulos D, Drosatos K, Hiyama Y, et al. MicroRNA-370 controls the expression of microRNA-122 and Cptlalpha and affects lipid metabolism [J]. Journal of lipid research,2010,51(6):1513-23.
[37]Gerin I, Bommer GT, McCoin CS, et al. Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis [J]. American journal of physiology Endocrinology and metabolism,2010,299(2):E198-206.
[38]Esau C, Kang X, Peralta E, et al. MicroRNA-143 regulates adipocyte differentiation [J]. The Journal of biological chemistry,2004,279(50):52361-5.
[39]Lin Q, Gao Z, Alarcon RM, et al. A role of miR-27 in the regulation of adipogenesis [J]. The FEBS journal,2009,276(8):2348-58.
[40]Nakanishi N, Nakagawa Y, Tokushige N, et al. The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice [J]. Biochemical and biophysical research communications, 2009,385(4):492-6.
[41]Thum T. MicroRNA therapeutics in cardiovascular medicine [J]. EMBO molecular medicine,2012,4(1):3-14.
[42]Chistiakov DA, Sobenin IA, Orekhov AN. Strategies to deliver microRNAs as potential therapeutics in the treatment of cardiovascular pathology [J]. Drug delivery,2012,19(8):392-405.
[43]van Rooij E, Olson EN. MicroRNAs:powerful new regulators of heart disease and provocative therapeutic targets [J]. The Journal of clinical investigation, 2007,117(9):2369-76.
[44]Thum T, Galuppo P, Wolf C, et al. MicroRNAs in the human heart:a clue to fetal gene reprogramming in heart failure [J]. Circulation,2007,116(3):258-67.
[45]Voellenkle C, van Rooij J, Cappuzzello C, et al. MicroRNA signatures in peripheral blood mononuclear cells of chronic heart failure patients [J]. Physiological genomics,2010,42(3):420-6.
[46]Fichtlscherer S, De Rosa S, Fox H, et al. Circulating microRNAs in patients with coronary artery disease [J]. Circulation research,2010,107(5):677-84.
[47]Jamaluddin MS, Weakley SM, Zhang L, et al. miRNAs:roles and clinical applications in vascular disease [J]. Expert review of molecular diagnostics,2011, 11(1):79-89.
[48]Sharp FR, Jickling GC, Stamova B, et al. Molecular markers and mechanisms of stroke:RNA studies of blood in animals and humans [J]. Journal of cerebral blood flow and metabolism:official journal of the International Society of Cerebral Blood Flow and Metabolism,2011,31 (7):1513-31.
[49]Jiang Q, Wang Y, Hao Y, et al. miR2Disease:a manually curated database for microRNA deregulation in human disease [J]. Nucleic acids research,2009, 37(Database issue):D98-104.
[2]Stein JH. Carotid intima-media thickness and vascular age:you are only as old as your arteries look [J]. Journal of the American Society of Echocardiography. official publication of the American Society of Echocardiography,2004,17(6):686-9.
[3]Bliss M. William Osler:a life in medicine [M]. Oxford University Press, 1999.
[4]世界卫生组织.2010年全球非传染性疾病现状报告,2011,日内瓦.
[5]卫生部心血管病防治研究中心.中国心血管病报告2011[M].中国大 百科全书出版社,2012.8.10.
[6]Alkerwi A, Guillaume M, Zannad F, et al. Nutrition, environment and cardiovascular health (NESCAV):protocol of an inter-regional cross-sectional study [J]. BMC public health,2010,10:698.
[7]世界卫生组织.心血管疾病预防心血管风险评估和管理袖珍指南[M].日内瓦,2008.
[8]Jashari F, Ibrahimi P, Nicoll R, et al. Coronary and carotid atherosclerosis: Similarities and differences [J]. Atherosclerosis,2013,227(2):193-200.
[9]Cohen Tervaert JW. Cardiovascular disease due to accelerated atherosclerosis in systemic vasculitides [J]. Best practice & research Clinical rheumatology,2013,27(1):33-44.
[10]Ference BA, Yoo W, Alesh I, et al. Effect of Long-Term Exposure to Lower Low-Density Lipoprotein Cholesterol Beginning Early in Life on the Risk of Coronary Heart Disease:A Mendelian Randomization Analysis [J]. Journal of the American College of Cardiology,2012,
[11]Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol:a meta-analysis of data from 170,000 participants in 26 randomised trials [J]. Lancet,2010,376(9753):1670-81.
[12]Goldstein JL, Brown MS. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia [J]. The Journal of biological chemistry,1974,249(16):5153-62.
[13]Musunuru K. Atherogenic dyslipidemia:cardiovascular risk and dietary intervention [J]. Lipids,2010,45(10):907-14.
[14]Weissglas-Volkov D, Pajukanta P. Genetic causes of high and low serum HDL-cholesterol [J]. Journal of lipid research,2010,51(8):2032-57.
[15]Rosenson RS, Brewer HB, Jr., Davidson WS, et al. Cholesterol efflux and atheroprotection:advancing the concept of reverse cholesterol transport [J]. Circulation,2012,125(15):1905-19.
[16]Badimon L, Vilahur G. LDL-cholesterol versus HDL-cholesterol in the atherosclerotic plaque:inflammatory resolution versus thrombotic chaos [J]. Annals of the New York Academy of Sciences,2012,1254:18-32.
[17]Mureddu GF, Brandimarte F, De Luca L. High-density lipoprotein levels and risk of cardiovascular events:a review [J]. J Cardiovasc Med (Hagerstown),2012, 13(9):575-86.
[18]Singh V, Sharma R, Kumar A, et al. Low high-density lipoprotein cholesterol:current status and future strategies for management [J]. Vascular health and risk management,2010,6:979-96.
[19]Tomkin GH. Atherosclerosis, diabetes and lipoproteins [J]. Expert review of cardiovascular therapy,2010,8(7):1015-29.
[20]Glomset JA. The metabolic role of lecithin:cholesterol acyltransferase: perspectives from pathology [J]. Advances in lipid research,1973,11(0):1-65.
[21]Brufau G, Groen AK, Kuipers F. Reverse cholesterol transport revisited: contribution of biliary versus intestinal cholesterol excretion [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2011,31(8):1726-33.
[22]Berrougui H, Khalil A. Age-associated decrease of high-density lipoprotein-mediated reverse cholesterol transport activity [J]. Rejuvenation research, 2009,12(2):117-26.
[23]Berrougui H, Momo CN, Khalil A. Health benefits of high-density lipoproteins in preventing cardiovascular diseases [J]. Journal of clinical lipidology, 2012,6(6):524-33.
[24]Fisher EA, Feig JE, Hewing B, et al. High-density lipoprotein function, dysfunction, and reverse cholesterol transport [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2012,32(12):2813-20.
[25]Eren E, Yilmaz N, Aydin O. High Density Lipoprotein and it's Dysfunction [J]. The open biochemistry journal,2012,6:78-93.
[26]Mackness B, Mackness M. The antioxidant properties of high-density lipoproteins in atherosclerosis [J]. Panminerva medica,2012,54(2):83-90.
[27]Boden WE. High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease:assessing the data from Framingham to the Veterans Affairs High--Density Lipoprotein Intervention Trial [J]. The American journal of cardiology,2000,86(12A):19L-22L.
[28]Barter P. HDL-C:role as a risk modifier [J]. Atherosclerosis Supplements, 2011,12(3):267-70.
[29]Lee JM, Choudhury RP. Atherosclerosis regression and high-density lipoproteins [J]. Expert review of cardiovascular therapy,2010,8(9):1325-34.
[30]Alwaili K, Awan Z, Alshahrani A, et al. High-density lipoproteins and cardiovascular disease:2010 update [J]. Expert review of cardiovascular therapy,2010, 8(3):413-23.
[31]Kapur NK, Ashen D, Blumenthal RS. High density lipoprotein cholesterol: an evolving target of therapy in the management of cardiovascular disease [J]. Vascular health and risk management,2008,4(1):39-57.
[32]Acton S, Rigotti A, Landschulz KT, et al. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor [J]. Science,1996,271(5248): 518-20.
[33]Rigotti A, Miettinen HE, Krieger M. The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues [J]. Endocrine reviews,2003,24(3):357-87.
[34]Saddar S, Mineo C, Shaul PW. Signaling by the high-affinity HDL receptor scavenger receptor B type I [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2010,30(2):144-50.
[35]Kocher O, Krieger M. Role of the adaptor protein PDZK1 in controlling the HDL receptor SR-BI [J]. Current opinion in lipidology,2009,20(3):236-41.
[36]Webb NR, de Villiers WJ, Connell PM, et al. Alternative forms of the scavenger receptor BI (SR-BI) [J]. Journal of lipid research,1997,38(7):1490-5.
[37]Glass C, Pittman RC, Weinstein DB, et al. Dissociation of tissue uptake of cholesterol ester from that of apoprotein A-I of rat plasma high density lipoprotein: selective delivery of cholesterol ester to liver, adrenal, and gonad [J]. Proceedings of the National Academy of Sciences of the United States of America,1983,80(17): 5435-9.
[38]Glass C, Pittman RC, Civen M, et al. Uptake of high-density lipoprotein-associated apoprotein A-I and cholesterol esters by 16 tissues of the rat in vivo and by adrenal cells and hepatocytes in vitro [J]. The Journal of biological chemistry,1985,260(2):744-50.
[39]Arai T, Wang N, Bezouevski M, et al. Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene [J]. The Journal of biological chemistry,1999,274(4):2366-71.
[40]Kozarsky KF, Donahee MH, Glick JM, et al. Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2000,20(3):721-7.
[41]Ueda Y, Gong E, Royer L, et al. Relationship between expression levels and atherogenesis in scavenger receptor class B, type I transgenics [J]. The Journal of biological chemistry,2000,275(27):20368-73.
[42]Zhang Y, Da Silva JR, Reilly M, et al. Hepatic expression of scavenger receptor class B type I (SR-BI) is a positive regulator of macrophage reverse cholesterol transport in vivo [J]. The Journal of clinical investigation,2005,115(10): 2870-4.
[43]Rader DJ, Alexander ET, Weibel GL, et al. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis [J]. Journal of lipid research,2009,50 Suppl:S189-94.
[44]Trigatti B, Rayburn H, Vinals M, et al. Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology [J]. Proceedings of the National Academy of Sciences of the United States of America, 1999,96(16):9322-7.
[45]Matoulkova E, Michalova E, Vojtesek B, et al. The role of the 3' untranslated region in post-transcriptional regulation of protein expression in mammalian cells [J]. RNA biology,2012,9(5):563-76.
[46]Bava FA, Eliscovich C, Ferreira PG, et al. CPEB1 coordinates alternative 3'-UTR formation with translational regulation [J]. Nature,2013,495(7439):121-5.
[47]Hoshino S. Mechanism of the initiation of mRNA decay:role of eRF3 family G proteins [J]. Wiley interdisciplinary reviews RNA,2012,3(6):743-57.
[48]Pichon X, Wilson LA, Stoneley M, et al. RNA binding protein/RNA element interactions and the control of translation [J]. Current protein & peptide science,2012,13(4):294-304.
[49]Adeli K. Translational control mechanisms in metabolic regulation: critical role of RNA binding proteins, microRNAs, and cytoplasmic RNA granules [J]. American journal of physiology Endocrinology and metabolism,2011,301(6): E1051-64.
[50]Barrett LW, Fletcher S, Wilton SD. Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements [J]. Cellular and molecular life sciences:CMLS,2012,69(21):3613-34.
[51]Chen W, Wang S, Ma Y, et al. Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response [J]. International journal of molecular medicine,2008,21(3): 345-53.
[52]Kong W, Wei J, Abidi P, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins [J]. Nature medicine, 2004,10(12):1344-51.
[53]Abidi P, Zhou Y, Jiang JD, et al. Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine [J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2005,25(10):2170-6.
[54]Lee S, Vasudevan S. Post-transcriptional stimulation of gene expression by microRNAs [J]. Advances in experimental medicine and biology,2013,768: 97-126.
[55]Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and function [J]. Thrombosis and haemostasis,2012,107(4):605-10.
[56]Mo YY. MicroRNA regulatory networks and human disease [J]. Cellular and molecular life sciences:CMLS,2012,69(21):3529-31.
[57]Iatan I, Palmyre A, Alrasheed S, et al. Genetics of cholesterol efflux [J]. Current atherosclerosis reports,2012,14(3):235-46.
[58]Sakurai F, Katayama K, Mizuguchi H. MicroRNA-regulated transgene expression systems for gene therapy and virotherapy [J]. Frontiers in bioscience:a journal and virtual library,2011,16:2389-401.
[l]司徒镇强,吴军正.细胞培养[M].世界图书出版公司,2007.
[2]Heckman KL, Pease LR. Gene splicing and mutagenesis by PCR-driven overlap extension [J]. Nature protocols,2007,2(4):924-32.
[3]Carl W. Dieffenbach GSD著,俞炜源,陈添弥译.PCR技术实验指南PCR Primer:A Laboratory Manual [M].第二版.科学出版社,2003.
[4]Frederick M. Ausubel RB, Robert E. Kingston, David D. Moore, J. G. Seidman, John A. Smith, Kevin Struhl,著,颜子颖王海林译.精编分子生物学实验指南Short Protocols in Molecular Biology [M].第五版：科学出版社,2008.
[5]John J. Sambrook DWR著.分子克隆实验指南Molecular Cloning:A Laboratory Manual [M].第三版：科学出版社,2002.
[6]Gu X, Lawrence R, Krieger M. Dissociation of the high density lipoprotein and low density lipoprotein binding activities of murine scavenger receptor class B type I (mSR-BI) using retrovirus library-based activity dissection [J]. The Journal of biological chemistry,2000,275(13):9120-30.
[7]Jurgens G, Xu QB, Huber LA, et al. Promotion of lymphocyte growth by high density lipoproteins (HDL). Physiological significance of the HDL binding site [J]. The Journal of biological chemistry,1989,264(15):8549-56.
[8]Traill KN, Jurgens G, Bock G, et al. High density lipoprotein uptake by freshly isolated human peripheral blood T lymphocytes [J]. Immunobiology,1987, 175(5):447-54.
[9]Xu Q, Buhler E, Steinmetz A, et al. A high-density-lipoprotein receptor appears to mediate the transfer of essential fatty acids from high-density lipoprotein to lymphocytes [J]. The Biochemical journal,1992,287 (Pt 2):395-401.
[10]Habelhah H, Frew IJ, Laine A, et al. Stress-induced decrease in TRAF2 stability is mediated by Siah2 [J]. The EMBO journal,2002,21(21):5756-65.
[11]Hughes R, Gilley J, Kristiansen M, et al. The MEK-ERK pathway negatively regulates bim expression through the 3'UTR in sympathetic neurons [J]. BMC neuroscience,2011,12:69.
[12]Shock JL, Fischer KF, DeRisi JL. Whole-genome analysis of mRNA decay in Plasmodium falciparum reveals a global lengthening of mRNA half-life during the intra-erythrocytic development cycle [J]. Genome biology,2007,8(7): R134.
[13]Wang Y, Hacker A, Murray-Stewart T, et al. Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein [J]. The Biochemical journal,2005,386(Pt 3):543-7.
[14]Chen C, Liang W, Jia J, et al. Aldosterone induces apoptosis in rat podocytes:role of PI3-K/Akt and p38MAPK signaling pathways [J]. Nephron Experimental nephrology,2009,113(1):e26-34.
[15]Chen S, Cheng AC, Wang MS, et al. Detection of apoptosis induced by new type gosling viral enteritis virus in vitro through fluorescein annexin V-FITC/PI double labeling [J]. World journal of gastroenterology:WJG,2008,14(14):2174-8.
[16]Kang X, Xie Q, Zhou X, et al. Effects of hepatitis B virus S protein exposure on sperm membrane integrity and functions [J]. PloS one,2012,7(3): e33471.
[17]Mattes MJ. Apoptosis assays with lymphoma cell lines:problems and pitfalls [J]. British journal of cancer,2007,96(6):928-36.
[1]Guttilla IK, White BA. Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells [J]. The Journal of biological chemistry, 2009,284(35):23204-16.
[2]Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis [J]. Nature,2005, 436(7048):214-20.
[3]Long D, Lee R, Williams P, et al. Potent effect of target structure on microRNA function [J]. Nature structural & molecular biology,2007,14(4):287-94.
[4]Matzura O, Wennborg A. RNAdraw:an integrated program for RNA secondary structure calculation and analysis under 32-bit Microsoft Windows [J]. Computer applications in the biosciences:CABIOS,1996,12(3):247-9.
[5]Reuter JS, Mathews DH. RNAstructure:software for RNA secondary structure prediction and analysis [J]. BMC bioinformatics,2010,11:129.
[6]Betel D, Koppal A, Agius P, et al. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites [J]. Genome biology,2010,11(8):R90.
[7]Betel D, Wilson M, Gabow A, et al. The microRNA.org resource:targets and expression [J]. Nucleic acids research,2008,36(Database issue):D149-53.
[8]John B, Enright AJ, Aravin A, et al. Human MicroRNA targets [J]. PLoS biology,2004,2(11):e363.
[9]Hu Z, Shen WJ, Kraemer FB, et al. MicroRNAs 125a and 455 repress lipoprotein-supported steroidogenesis by targeting scavenger receptor class B type I in steroidogenic cells [J]. Molecular and cellular biology,2012,32(24):5035-45.
[10]Larkin MA, Blackshields G, Brown NP, et al. Clustal W and Clustal X version 2.0 [J]. Bioinformatics,2007,23(21):2947-8.
[11]Crooks GE, Hon G, Chandonia JM, et al. WebLogo:a sequence logo generator [J]. Genome research,2004,14(6):1188-90.
[12]Chinetti G, Gbaguidi FG, Griglio S, et al. CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors [J]. Circulation,2000,101(20):2411-7.
[13]Tiwari RL, Singh V, Barthwal MK. Macrophages:an elusive yet emerging therapeutic target of atherosclerosis [J]. Medicinal research reviews,2008, 28(4):483-544.
[14]Covey SD, Krieger M, Wang W, et al. Scavenger receptor class B type I-mediated protection against atherosclerosis in LDL receptor-negative mice involves its expression in bone marrow-derived cells [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2003,23(9):1589-94.
[15]Zhao GJ, Yin K, Fu YC, et al. The interaction of ApoA-I and ABCA1 triggers signal transduction pathways to mediate efflux of cellular lipids [J]. Mol Med, 2012,18:149-58.
[16]Iatan I, Palmyre A, Alrasheed S, et al. Genetics of cholesterol efflux [J]. Current atherosclerosis reports,2012,14(3):235-46.
[17]Liu Y, Tang C. Regulation of ABCA1 functions by signaling pathways [J]. Biochimica et biophysica acta,2012,1821(3):522-9.
[18]Buechler C, Bauer S. ATP binding cassette transporter A1 (ABCA1) associated proteins:potential drug targets in the metabolic syndrome and atherosclerotic disease? [J]. Current pharmaceutical biotechnology,2012,13(2): 319-30.
[19]Charlton-Menys V, Durrington PN. Human cholesterol metabolism and therapeutic molecules [J]. Experimental physiology,2008,93(1):27-42.
[20]Yao RE, Wang J, Geng J, et al. Identification of LDLR mutations in two Chinese pedigrees with familial hypercholesterolemia [J]. Journal of pediatric endocrinology & metabolism:JPEM,2012,25(7-8):769-73.
[21]Skalen K, Gustafsson M, Rydberg EK, et al. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis [J]. Nature,2002,417(6890):750-4.
[22]Sorrentino V, Zelcer N. Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor [J]. Current opinion in lipidology,2012,23(3):213-9.
[23]Dekkers JF, van der Ent CK, Kalkhoven E, et al. PPARgamma as a therapeutic target in cystic fibrosis [J]. Trends in molecular medicine,2012,18(5): 283-91.
[24]Floyd ZE, Stephens JM. Controlling a master switch of adipocyte development and insulin sensitivity:covalent modifications of PPARgamma [J]. Biochimica et biophysica acta,2012,1822(7):1090-5.
[25]Abbas A, Blandon J, Rude J, et al. PPAR-gamma agonist in treatment of diabetes:cardiovascular safety considerations [J]. Cardiovascular & hematological agents in medicinal chemistry,2012,10(2):124-34.
[26]Lamers C, Schubert-Zsilavecz M, Merk D. Therapeutic modulators of peroxisome proliferator-activated receptors (PPAR):a patent review (2008-present) [J]. Expert opinion on therapeutic patents,2012,22(7):803-41.
[27]Cariou B, Charbonnel B, Staels B. Thiazolidinediones and PPARgamma agonists:time for a reassessment [J]. Trends in endocrinology and metabolism:TEM, 2012,23(5):205-15.
[28]Agrawal R, Jain P, Dikshit SN. Balaglitazone:a second generation peroxisome proliferator-activated receptor (PPAR) gamma (gamma) agonist [J]. Mini reviews in medicinal chemistry,2012,12(2):87-97.
[29]Huang JV, Greyson CR, Schwartz GG. PPAR-gamma as a therapeutic target in cardiovascular disease:evidence and uncertainty [J]. Journal of lipid research, 2012,53(9):1738-54.
[30]Ciudin A, Hernandez C, Simo R. Update on cardiovascular safety of PPARgamma agonists and relevance to medicinal chemistry and clinical pharmacology [J]. Current topics in medicinal chemistry,2012,12(6):585-604.
[31]Balakumar P, Kathuria S. Submaximal PPARgamma activation and endothelial dysfunction:new perspectives for the management of cardiovascular disorders [J]. British journal of pharmacology,2012,166(7):1981-92.
[32]Rottiers V, Naar AM. MicroRNAs in metabolism and metabolic disorders [J]. Nature reviews Molecular cell biology,2012,13(4):239-50.
[33]Rottiers V, Najafi-Shoushtari SH, Kristo F, et al. MicroRNAs in metabolism and metabolic diseases [J]. Cold Spring Harbor symposia on quantitative biology,2011,76:225-33.
[34]Ambros V. The functions of animal microRNAs [J]. Nature,2004, 431(7006):350-5.
[35]Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease [J]. Circulation,2010,121(8):1022-32.
[36]Suarez Y, Sessa WC. MicroRNAs as novel regulators of angiogenesis [J]. Circulation research,2009,104(4):442-54.
[37]Perera RJ, Ray A. MicroRNAs in the search for understanding human diseases [J]. BioDrugs:clinical immunotherapeutics, biopharmaceuticals and gene therapy,2007,21(2):97-104.
[38]O'Neill LA, Sheedy FJ, McCoy CE. MicroRNAs:the fine-tuners of Toll-like receptor signalling [J]. Nature reviews Immunology,2011,11(3):163-75.
[39]Ha TY. MicroRNAs in Human Diseases:From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases [J]. Immune network,2011,11(5): 227-44.
[40]Ha TY. MicroRNAs in Human Diseases:From Cancer to Cardiovascular Disease [J]. Immune network,2011,11(3):135-54.
[41]Pallante P, Visone R, Croce CM, et al. Deregulation of microRNA expression in follicular-cell-derived human thyroid carcinomas [J]. Endocrine-related cancer,2010,17(1):F91-104.
[42]Belver L, de Yebenes VG, Ramiro AR. MicroRNAs prevent the generation of autoreactive antibodies [J]. Immunity,2010,33(5):713-22.
[43]Najafi-Shoushtari SH. MicroRNAs in cardiometabolic disease [J]. Current atherosclerosis reports,2011,13(3):202-7.
[44]Fernandez-Hernando C, Suarez Y, Rayner KJ, et al. MicroRNAs in lipid metabolism [J]. Current opinion in lipidology,2011,22(2):86-92.
[45]Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting [J]. Cell metabolism,2006,3(2): 87-98.
[46]Najafi-Shoushtari SH, Kristo F, Li Y, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis [J]. Science,2010,328(5985): 1566-9.
[47]Rayner KJ, Suarez Y, Davalos A, et al. MiR-33 contributes to the regulation of cholesterol homeostasis [J]. Science,2010,328(5985):1570-3.
[48]Ramirez CM, Davalos A, Goedeke L, et al. MicroRNA-758 regulates cholesterol efflux through posttranscriptional repression of ATP-binding cassette transporter A1 [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2011,31(11): 2707-14.
[49]Vickers KC, Palmisano BT, Shoucri BM, et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins [J]. Nature cell biology,2011,13(4):423-33.
[50]Trigatti BL, Krieger M, Rigotti A. Influence of the HDL receptor SR-BI on lipoprotein metabolism and atherosclerosis [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2003,23(10):1732-8.
[51]Zhang X, Moor AN, Merkler KA, et al. Regulation of alternative splicing of liver scavenger receptor class B gene by estrogen and the involved regulatory splicing factors [J]. Endocrinology,2007,148(11):5295-304.
[52]Leiva A, Verdejo H, Benitez ML, et al. Mechanisms regulating hepatic SR-BI expression and their impact on HDL metabolism [J]. Atherosclerosis,2011, 217(2):299-307.
[53]Hirano K, Ikegami C, Tsujii K, et al. Probucol enhances the expression of human hepatic scavenger receptor class B type I, possibly through a species-specific mechanism [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2005,25(11): 2422-7.
[54]Shetty S, Eckhardt ER, Post SR, et al. Phosphatidylinositol-3-kinase regulates scavenger receptor class B type I subcellular localization and selective lipid uptake in hepatocytes [J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2006, 26(9):2125-31.
[55]Krek A, Grun D, Poy MN, et al. Combinatorial microRNA target predictions [J]. Nature genetics,2005,37(5):495-500.
[56]Thomas M, Lieberman J, Lal A. Desperately seeking microRNA targets [J]. Nature structural & molecular biology,2010,17(10):1169-74.
[57]Yesilaltay A, Daniels K, Pal R, et al. Loss of PDZK1 causes coronary artery occlusion and myocardial infarction in Paigen diet-fed apolipoprotein E deficient mice [J]. PloS one,2009,4(12):e8103.
[58]Huby T, Doucet C, Dachet C, et al. Knockdown expression and hepatic deficiency reveal an atheroprotective role for SR-BI in liver and peripheral tissues [J]. The Journal of clinical investigation,2006,116(10):2767-76.
[59]Ji A, Meyer JM, Cai L, et al. Scavenger receptor SR-BI in macrophage lipid metabolism [J]. Atherosclerosis,2011,217(1):106-12.
[60]Yvan-Charvet L, Wang N, Tall AR. Role of HDL, ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses [J]. Arteriosclerosis, thrombosis, and vascular biology,2010,30(2):139-43.
[61]Zhang Z, Tang H, Wang Z, et al. MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma [J]. Molecular cancer,2011,10(124.
[62]Liu M, Lang N, Chen X, et al. miR-185 targets RhoA and Cdc42 expression and inhibits the proliferation potential of human colorectal cells [J]. Cancer letters,2011,301(2):151-60.
[63]Kuhn S, Johnson SL, Furness DN, et al. miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells [J]. Proceedings of the National Academy of Sciences of the United States of America,2011,108(6): 2355-60.
[64]Johnnidis JB, Harris MH, Wheeler RT, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223 [J]. Nature,2008,451(7182): 1125-9.
[65]Zhuang G, Meng C, Guo X, et al. A novel regulator of macrophage activation:miR-223 in obesity-associated adipose tissue inflammation [J]. Circulation, 2012,125(23):2892-903.
[66]Xu XM, Qian JC, Deng ZL, et al. Expression of miR-21, miR-31, miR-96 and miR-135b is correlated with the clinical parameters of colorectal cancer [J]. Oncology letters,2012,4(2):339-45.
[67]Lin H, Dai T, Xiong H, et al. Unregulated miR-96 induces cell proliferation in human breast cancer by downregulating transcriptional factor FOXO3a [J]. PloS one,2010,5(12):e15797.
[68]Li J, Guo Y, Liang X, et al. MicroRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4 [J]. Journal of cancer research and clinical oncology,2012,138(5):763-74.
[69]Zeng X, Xiang J, Wu M, et al. Circulating miR-17, miR-20a, miR-29c, and miR-223 combined as non-invasive biomarkers in nasopharyngeal carcinoma [J]. PloS one,2012,7(10):e46367.
[70]Ebert KM, Paynton BV, McKnight GS, et al. Translation and stability of ovalbumin messenger RNA injected into growing oocytes and fertilized ova of mice [J]. Journal of embryology and experimental morphology,1984,84:91-103.
[71]Leys EJ, Crouse GF, Kellems RE. Dihydrofolate reductase gene expression in cultured mouse cells is regulated by transcript stabilization in the nucleus [J]. The Journal of cell biology,1984,99(1 Pt 1):180-7.
[72]Dani C, Mechti N, Piechaczyk M, et al. Increased rate of degradation of c-myc mRNA in interferon-treated Daudi cells [J]. Proceedings of the National Academy of Sciences of the United States of America,1985,82(15):4896-9.
[73]Kislauskis EH, Li Z, Singer RH, et al. Isoform-specific 3'-untranslated sequences sort alpha-cardiac and beta-cytoplasmic actin messenger RNAs to different cytoplasmic compartments [J]. The Journal of cell biology,1993,123(1):165-72.
[74]Kislauskis EH, Zhu X, Singer RH. Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype [J]. The Journal of cell biology,1994,127(2):441-51.
[75]Suay L, Salvador ML, Abesha E, et al. Specific roles of 5'RNA secondary structures in stabilizing transcripts in chloroplasts [J]. Nucleic acids research,2005,33(15):4754-61.
[76]Ross J. Control of messenger RNA stability in higher eukaryotes [J]. Trends in genetics:TIG,1996,12(5):171-5.
[77]Gutierrez RA, Macintosh GC, Green PJ. Current perspectives on mRNA stability in plants:multiple levels and mechanisms of control [J]. Trends in plant science,1999,4(11):429-38.
[78]Mitchell P, Tollervey D. mRNA turnover [J]. Current opinion in cell biology,2001,13(3):320-5.
[79]Huang HW, Payne DE, Bi W, et al. Sequences of a hairpin structure in the 3'-untranslated region mediate regulation of human pulmonary surfactant protein B mRNA stability [J]. American journal of physiology Lung cellular and molecular physiology,2012,302(10):L1107-17.
[80]Anant S, Davidson NO. An AU-rich sequence element (UUUN[A/U]U) downstream of the edited C in apolipoprotein B mRNA is a high-affinity binding site for Apobec-1:binding of Apobec-1 to this motif in the 3'untranslated region of c-myc increases mRNA stability [J]. Molecular and cellular biology,2000,20(6):1982-92.
[81]Paschoud S, Dogar AM, Kuntz C, et al. Destabilization of interleukin-6 mRNA requires a putative RNA stem-loop structure, an AU-rich element, and the RNA-binding protein AUF1 [J]. Molecular and cellular biology,2006,26(22): 8228-41.
[82]Guhaniyogi J, Brewer G. Regulation of mRNA stability in mammalian cells [J]. Gene,2001,265(1-2):11-23.
[83]Gaspar P, Moura G, Santos MA, et al. mRNA secondary structure optimization using a correlated stem-loop prediction [J]. Nucleic acids research,2013, 41(6):e73.
[84]Bolukbasi MF, Mizrak A, Ozdener GB, et al. miR-1289 and "Zipcode"-like Sequence Enrich mRNAs in Microvesicles [J]. Molecular therapy Nucleic acids,2012,1:e 10.
[85]Zhang M, Lam TT, Tonelli M, et al. Interaction of the histone mRNA hairpin with stem-loop binding protein (SLBP) and regulation of the SLBP-RNA complex by phosphorylation and proline isomerization [J]. Biochemistry,2012,51(15): 3215-31.
[86]Tan D, Marzluff WF, Dominski Z, et al. Structure of histone mRNA stem-loop, human stem-loop binding protein, and 3'hExo ternary complex [J]. Science, 2013,339(6117):318-21.
[1]Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 [J]. Cell,1993, 75(5):843-54.
[2]Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans [3]. Cell,1993,75(5):855-62.
[3]Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans [J]. Nature,2000, 403(6772):901-6.
[4]Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets [J]. Cell, 2005,120(1):15-20.
[5]Sandhu SK, Croce CM, Garzon R. Micro-RNA Expression and Function in Lymphomas [J]. Advances in hematology,2011,2011:347137.
[6]Ambros V. The functions of animal microRNAs [J]. Nature,2004, 431(7006):350-5.
[7]Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function [J].Cell,2004,116(2):281-97.
[8]Cordes KR, Srivastava D, Ivey KN. MicroRNAs in cardiac development [J]. Pediatric cardiology,2010,31(3):349-56.
[9]Lagos-Quintana M, Rauhut R, Lendeckel W, et al. Identification of novel genes coding for small expressed RNAs [J]. Science,2001,294(5543):853-8.
[10]Lau NC, Lim LP, Weinstein EG, et al. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans [J]. Science,2001,294(5543): 858-62.
[11]Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans [J]. Science,2001,294(5543):862-4.
[12]Ambros V, Bartel B, Bartel DP, et al. A uniform system for microRNA annotation [J]. RNA,2003,9(3):277-9.
[13]Griffiths-Jones S, Grocock RJ, van Dongen S, et al. miRBase:microRNA sequences, targets and gene nomenclature [J]. Nucleic acids research,2006, 34(Database issue):D140-4.
[14]Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology [J]. Nature,2011,469(7330):336-42.
[15]Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease [J]. Circulation,2010,121(8):1022-32.
[16]Ji R, Cheng Y, Yue J, et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation [J]. Circulation research,2007,100(11):1579-88.
[17]Elia L, Quintavalle M, Zhang J, et al. The knockout of miR-143 and-145 alters smooth muscle cell maintenance and vascular homeostasis in mice:correlates with human disease [J]. Cell death and differentiation,2009,16(12):1590-8.
[18]Cheng Y, Liu X, Yang J, et al. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation [J]. Circulation research,2009,105(2):158-66.
[19]Xu S, Jin C, Shen X, et al. MicroRNAs as potential novel therapeutic targets and tools for regulating paracrine function of endothelial progenitor cells [J]. Medical science monitor:international medical journal of experimental and clinical research,2012,18(7):HY27-31.
[20]Little PJ, Ballinger ML, Osman N. Vascular wall proteoglycan synthesis and structure as a target for the prevention of atherosclerosis [J]. Vascular health and risk management,2007,3(1):117-24.
[21]Glass CK, Witztum JL. Atherosclerosis. the road ahead [J]. Cell,2001, 104(4):503-16.
[22]Ross R. Atherosclerosis--an inflammatory disease [J]. The New England journal of medicine,1999,340(2):115-26.
[23]Vickers KC, Remaley AT. MicroRNAs in atherosclerosis and lipoprotein metabolism [J]. Current opinion in endocrinology, diabetes, and obesity,2010,17(2): 150-5.
[24]Widlansky ME, Gokce N, Keaney JF, Jr., et al. The clinical implications of endothelial dysfunction [J]. Journal of the American College of Cardiology,2003, 42(7):1149-60.
[25]Endemann DH, Schiffrin EL. Endothelial dysfunction [J]. Journal of the American Society of Nephrology:JASN,2004,15(8):1983-92.
[26]Kuehbacher A, Urbich C, Zeiher AM, et al. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis [J]. Circulation research,2007, 101(1):59-68.
[27]Minami Y, Satoh M, Maesawa C, et al. Effect of atorvastatin on microRNA 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease [J]. European journal of clinical investigation,2009, 39(5):359-67.
[28]Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway [J]. The Journal of clinical investigation,2001,108(3):391-7.
[29]Hulsmans M, De Keyzer D, Holvoet P. MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis [J]. FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 2011,25(8):2515-27.
[30]Lynn FC. Meta-regulation:microRNA regulation of glucose and lipid metabolism [J]. Trends in endocrinology and metabolism:TEM,2009,20(9):452-9.
[31]Dietschy JM, Turley SD. Control of cholesterol turnover in the mouse [J]. The Journal of biological chemistry,2002,277(6):3801-4.
[32]Chen XM. MicroRNA signatures in liver diseases [J]. World journal of gastroenterology:WJG,2009,15(14):1665-72.
[33]Fernandez-Hernando C, Suarez Y, Rayner KJ, et al. MicroRNAs in lipid metabolism [J]. Current opinion in lipidology,2011,22(2):86-92.
[34]Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting [J]. Cell metabolism,2006,3(2): 87-98.
[35]Elmen J, Lindow M, Schutz S, et al. LNA-mediated microRNA silencing in non-human primates [J]. Nature,2008,452(7189):896-9.
[36]Iliopoulos D, Drosatos K, Hiyama Y, et al. MicroRNA-370 controls the expression of microRNA-122 and Cptlalpha and affects lipid metabolism [J]. Journal of lipid research,2010,51(6):1513-23.
[37]Gerin I, Bommer GT, McCoin CS, et al. Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis [J]. American journal of physiology Endocrinology and metabolism,2010,299(2):E198-206.
[38]Esau C, Kang X, Peralta E, et al. MicroRNA-143 regulates adipocyte differentiation [J]. The Journal of biological chemistry,2004,279(50):52361-5.
[39]Lin Q, Gao Z, Alarcon RM, et al. A role of miR-27 in the regulation of adipogenesis [J]. The FEBS journal,2009,276(8):2348-58.
[40]Nakanishi N, Nakagawa Y, Tokushige N, et al. The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice [J]. Biochemical and biophysical research communications, 2009,385(4):492-6.
[41]Thum T. MicroRNA therapeutics in cardiovascular medicine [J]. EMBO molecular medicine,2012,4(1):3-14.
[42]Chistiakov DA, Sobenin IA, Orekhov AN. Strategies to deliver microRNAs as potential therapeutics in the treatment of cardiovascular pathology [J]. Drug delivery,2012,19(8):392-405.
[43]van Rooij E, Olson EN. MicroRNAs:powerful new regulators of heart disease and provocative therapeutic targets [J]. The Journal of clinical investigation, 2007,117(9):2369-76.
[44]Thum T, Galuppo P, Wolf C, et al. MicroRNAs in the human heart:a clue to fetal gene reprogramming in heart failure [J]. Circulation,2007,116(3):258-67.
[45]Voellenkle C, van Rooij J, Cappuzzello C, et al. MicroRNA signatures in peripheral blood mononuclear cells of chronic heart failure patients [J]. Physiological genomics,2010,42(3):420-6.
[46]Fichtlscherer S, De Rosa S, Fox H, et al. Circulating microRNAs in patients with coronary artery disease [J]. Circulation research,2010,107(5):677-84.
[47]Jamaluddin MS, Weakley SM, Zhang L, et al. miRNAs:roles and clinical applications in vascular disease [J]. Expert review of molecular diagnostics,2011, 11(1):79-89.
[48]Sharp FR, Jickling GC, Stamova B, et al. Molecular markers and mechanisms of stroke:RNA studies of blood in animals and humans [J]. Journal of cerebral blood flow and metabolism:official journal of the International Society of Cerebral Blood Flow and Metabolism,2011,31 (7):1513-31.
[49]Jiang Q, Wang Y, Hao Y, et al. miR2Disease:a manually curated database for microRNA deregulation in human disease [J]. Nucleic acids research,2009, 37(Database issue):D98-104.
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