鞘磷脂类信号通路与动脉粥样硬化的研究进展
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摘要
动脉粥样硬化是临床常见的冠心病和脑梗死等缺血性心脑血管疾病的主要病理基础,其病因复杂,发病机制尚未完全阐明。近年来,越来越多的研究显示鞘磷脂类信号通路可通过调节脂代谢、炎症和血管内皮功能等影响动脉粥样硬化的发生发展。文章综述了鞘磷脂类信号通路关键分子鞘磷脂、神经酰胺和1-磷酸鞘氨醇与动脉粥样硬化的关系,旨在为防治疾病提供新思路。
Atherosclerosis(As) is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases such as coronary heart disease and cerebral infarction.Its etiology is complicated and the pathogenesis has not been fully clarified.In recent years,more and more studies revealed that sphingomyelin signaling pathway can affect the occurrence and development of atherosclerosis by regulating lipid metabolism,inflammation and vascular endothelial function.This paper reviews the relationship between sphingomyelin,ceramide and sphingosine-1-phosphate,the key molecules of sphingomyelin signaling pathway,and atherosclerosis in order to provide new ideas for the prevention and treatment of As.
Atherosclerosis(As) is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases such as coronary heart disease and cerebral infarction.Its etiology is complicated and the pathogenesis has not been fully clarified.In recent years,more and more studies revealed that sphingomyelin signaling pathway can affect the occurrence and development of atherosclerosis by regulating lipid metabolism,inflammation and vascular endothelial function.This paper reviews the relationship between sphingomyelin,ceramide and sphingosine-1-phosphate,the key molecules of sphingomyelin signaling pathway,and atherosclerosis in order to provide new ideas for the prevention and treatment of As.
引文
[1]舒刘芳,姜希娟,杨琳,等.血管平滑肌细胞表型转换对动脉粥样硬化的作用研究进展[J].中国动脉硬化杂志,2018,26(1):99-102.
[2]李靓,谢巍,姜志胜,等.我国动脉粥样硬化基础研究近三年进展[J].中国动脉硬化杂志,2015,23(11):1182-1188.
[3]马彩云,柳景华,王韶屏,等.内皮功能障碍与冠心病的研究[J].心肺血管病杂志,2016,35(6):482-484.
[4]易吉平,曾明,何兴轩.鞘磷脂类信号通路在肺纤维化发病机制中的作用[J].中国药理学与毒理学杂志,2016,30(2):158-164.
[5]Maceyka M,Spiegel S.Sphingolipid metabolites in inflammatory disease[J].Nature,2014,510(7503):58-67.
[6]Edsfeldt A,Dunér P,Sthlman M,et al.Sphingolipids contribute to human atherosclerotic plaque inflammation[J].Arterioscler Thromb Vasc Biol,2016,36(6):1132-1140.
[7]Hammad SM,Pierce JS,Soodavar F,et al.Blood sphingolipidomics in healthy humans:impact of sample collection methodology[J].J Lipid Res,2010,51(10):3074-3087.
[8]Zakiev ER,Sukhorukov VN,Melnichenko AA,et al.Lipid composition of circulating multiple-modified low density lipoprotein[J].Lipids Health Dis,2016,15(1):134.
[9]Liu J,Huan CM,Chakraborty M,et al.Macrophage sphingomyelin synthase 2(SMS2)deficiency decreases atherosclerosis in mice[J].Circ Res,2009,105(3):295-303.
[10]Schlitt A,Blankenberg S,Yan DG,et al.Further evaluation of plasma sphingomyelin levels as a risk factor for coronary[J].Nutr Metab(Lond),2006,3:5.
[11]王尹曼,陈学颖,徐磊,等.鞘磷脂与冠状动脉粥样硬化性心脏病患者冠状动脉狭窄程度的相关性研究[J].中国临床医学,2015,22(3):310-313,317.
[12]秦睿,陈明亮,朱珂,等.神经鞘磷脂合成酶2基因的缺失有抗动脉粥样硬化及抗炎作用[J].生理学报,2010,62(4):333-338.
[13]薛婧.鞘磷脂合成酶2缺乏对小鼠脑缺血再灌注损伤后炎症反应的影响及其机制研究[D].河北医科大学,2017.
[14]Cal L,Oyeniran C,Biwas D D,et al.ORMDL proteins regulate ceramide levels during sterile inflammation[J].JLipid Res,2016,57(8):1412-1422.
[15]Boon J,Hoy A J,Stark R,et al.Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance[J].Diabetes,2013,62(2):401-410.
[16]Li C,Zhou JL,Wang AM,et al.Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats[J].Diabetes Res Clin Pract,2011,93(1):77-85.
[17]Kasumov T,Li L,Li M,et al.Ceramide as a mediator of non-alcoholic fatty liver disease and associated atherosclerosis[J].PLos One,2015,10(5):e0126910.
[18]Kasumov T,Li L,Previs S,et al.Abstract 650:ceramide as a mediator of insulin resistance-associated atherosclerosis[J].Arterioscler Thromb Vasc Biol,2014,34:A650.
[19]Ohanian J,Liao AY,Ohanian SP.Age-related remodeling of small arteries is accompanied by increased sphingomyelinase activity and accumulation of long-chain ceramides[J].Physiol Rep,2014,2(5):e12015.
[20]程耀萍.酸性鞘磷脂酶/神经酰胺通路介导模拟失重大鼠颈总动脉功能与结构重塑[D].第四军医大学,2015.
[21]Cheng JM,Suoniemi M,Kardys I,et al.Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome:results of the ATHEROREMO-IVUS study[J].Atherosclerosis,2015,243(2):560-566.
[22]Taniguchi M,Kitatani K,Kondo T,et al.Regulation of autophagy and its associated cell death by“sphingolipid rheostat”:reciprocal role of ceramide and sphingosine 1-phosphate in the mammalian target of rapamycin pathway[J].J Biol Chem,2012,287(47):39898-39910.
[23]Blaho VA,Hla T.An update on the biology of sphingosine1-phosphate receptors[J].J Lipid Res,2014,55(8):1596-1608.
[24]Christoffersen C,Obinata H,Kumaraswamy SB,et al.Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M[J].Proc Natl Acad Sci USA,2011,108(23):9613-9618.
[25]Ruiz M,Frej C,Holmer A,et al.High-density lipoprotein associated apolipoprotein M limits endothelial inflammation by delivering sphingosine-1-phosphate to the sphingosine-1-phosphate receptor 1[J].Arterioscler Thromb Vasc Biol,2017,37(1):118-129.
[26]Wilkerson BA,Grass GD,Wing SB,et al.Sphingosine 1-phosphate(S1P)carrier-dependent regulation of endothelial barrier:high density lipoprotein(HDL)-S1P prolongs endothelial barrier enhancement as compared with albuminS1P via effects on levels,trafficking,and signaling of S1P1[J].J Biol Chem,2012,287(53):44645-44653.
[27]Yamamoto R,Aoki T,Koseki H,et al.A sphingosine-1-phosphate receptor type 1 agonist,ASP4058,suppresses intracranial aneurysm through promoting endothelial integrity and blocking macrophage transmigration[J].Br J Pharmacol,2017,174(13):2085.
[28]Galvani S,Sanson M,Blaho VA,et al.HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation[J].Sci Signal,2015,8(389):ra79.
[29]Zhang G,Yang L,Kim GS,et al.Critical role of sphingosine-1-phosphate receptor 2(S1PR2)in acute vascular inflammation[J].Blood,2013,122(3):443-455.
[30]Liu W,Liu B,Liu S,et al.Sphingosine-1-phosphate receptor 2 mediates endothelial cells dysfunction by PI3K-Akt pathway under high glucose condition[J].Eur J Pharmacol,2016,776:19-25.
[31]Zhang W,An J,Jawadi H,et al.Sphingosine-1-phosphate receptor-2 mediated NF-κB activation contributes to tumor necrosis factor-αinduced VCAM-1 and ICAM-1 expression in endothelial cells[J].Prostaglandins Other Lipid Mediat,2013,106:62-71.
[32]Wang F,Okamoto Y,Inoki I,et al.Sphingosine-1-phosphate receptor-2 deficiency leads to inhibition of macrophage proinflammatory activities and atherosclerosis in apo E-deficient mice[J].J Clin Invest,2010,120(11):3979-3995.
[33]T9lle M,Klockl L,Wiedon A,et al.Regulation of endothelial nitric oxide synthase activation in endothelial cells by S1P1 and S1P3[J].Biochem Biophys Res Commun,2016,476(4):627-634.
[34]Lin CC,Lee IT,Hsu CH,et al.Sphingosine-1-phosphate mediates ICAM-1-dependent monocyte adhesion through p38 MAPK and p42/p44 MAPK-dependent Akt activation[J].PLoS One,2015,10(3):e0118473.
[2]李靓,谢巍,姜志胜,等.我国动脉粥样硬化基础研究近三年进展[J].中国动脉硬化杂志,2015,23(11):1182-1188.
[3]马彩云,柳景华,王韶屏,等.内皮功能障碍与冠心病的研究[J].心肺血管病杂志,2016,35(6):482-484.
[4]易吉平,曾明,何兴轩.鞘磷脂类信号通路在肺纤维化发病机制中的作用[J].中国药理学与毒理学杂志,2016,30(2):158-164.
[5]Maceyka M,Spiegel S.Sphingolipid metabolites in inflammatory disease[J].Nature,2014,510(7503):58-67.
[6]Edsfeldt A,Dunér P,Sthlman M,et al.Sphingolipids contribute to human atherosclerotic plaque inflammation[J].Arterioscler Thromb Vasc Biol,2016,36(6):1132-1140.
[7]Hammad SM,Pierce JS,Soodavar F,et al.Blood sphingolipidomics in healthy humans:impact of sample collection methodology[J].J Lipid Res,2010,51(10):3074-3087.
[8]Zakiev ER,Sukhorukov VN,Melnichenko AA,et al.Lipid composition of circulating multiple-modified low density lipoprotein[J].Lipids Health Dis,2016,15(1):134.
[9]Liu J,Huan CM,Chakraborty M,et al.Macrophage sphingomyelin synthase 2(SMS2)deficiency decreases atherosclerosis in mice[J].Circ Res,2009,105(3):295-303.
[10]Schlitt A,Blankenberg S,Yan DG,et al.Further evaluation of plasma sphingomyelin levels as a risk factor for coronary[J].Nutr Metab(Lond),2006,3:5.
[11]王尹曼,陈学颖,徐磊,等.鞘磷脂与冠状动脉粥样硬化性心脏病患者冠状动脉狭窄程度的相关性研究[J].中国临床医学,2015,22(3):310-313,317.
[12]秦睿,陈明亮,朱珂,等.神经鞘磷脂合成酶2基因的缺失有抗动脉粥样硬化及抗炎作用[J].生理学报,2010,62(4):333-338.
[13]薛婧.鞘磷脂合成酶2缺乏对小鼠脑缺血再灌注损伤后炎症反应的影响及其机制研究[D].河北医科大学,2017.
[14]Cal L,Oyeniran C,Biwas D D,et al.ORMDL proteins regulate ceramide levels during sterile inflammation[J].JLipid Res,2016,57(8):1412-1422.
[15]Boon J,Hoy A J,Stark R,et al.Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance[J].Diabetes,2013,62(2):401-410.
[16]Li C,Zhou JL,Wang AM,et al.Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats[J].Diabetes Res Clin Pract,2011,93(1):77-85.
[17]Kasumov T,Li L,Li M,et al.Ceramide as a mediator of non-alcoholic fatty liver disease and associated atherosclerosis[J].PLos One,2015,10(5):e0126910.
[18]Kasumov T,Li L,Previs S,et al.Abstract 650:ceramide as a mediator of insulin resistance-associated atherosclerosis[J].Arterioscler Thromb Vasc Biol,2014,34:A650.
[19]Ohanian J,Liao AY,Ohanian SP.Age-related remodeling of small arteries is accompanied by increased sphingomyelinase activity and accumulation of long-chain ceramides[J].Physiol Rep,2014,2(5):e12015.
[20]程耀萍.酸性鞘磷脂酶/神经酰胺通路介导模拟失重大鼠颈总动脉功能与结构重塑[D].第四军医大学,2015.
[21]Cheng JM,Suoniemi M,Kardys I,et al.Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome:results of the ATHEROREMO-IVUS study[J].Atherosclerosis,2015,243(2):560-566.
[22]Taniguchi M,Kitatani K,Kondo T,et al.Regulation of autophagy and its associated cell death by“sphingolipid rheostat”:reciprocal role of ceramide and sphingosine 1-phosphate in the mammalian target of rapamycin pathway[J].J Biol Chem,2012,287(47):39898-39910.
[23]Blaho VA,Hla T.An update on the biology of sphingosine1-phosphate receptors[J].J Lipid Res,2014,55(8):1596-1608.
[24]Christoffersen C,Obinata H,Kumaraswamy SB,et al.Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M[J].Proc Natl Acad Sci USA,2011,108(23):9613-9618.
[25]Ruiz M,Frej C,Holmer A,et al.High-density lipoprotein associated apolipoprotein M limits endothelial inflammation by delivering sphingosine-1-phosphate to the sphingosine-1-phosphate receptor 1[J].Arterioscler Thromb Vasc Biol,2017,37(1):118-129.
[26]Wilkerson BA,Grass GD,Wing SB,et al.Sphingosine 1-phosphate(S1P)carrier-dependent regulation of endothelial barrier:high density lipoprotein(HDL)-S1P prolongs endothelial barrier enhancement as compared with albuminS1P via effects on levels,trafficking,and signaling of S1P1[J].J Biol Chem,2012,287(53):44645-44653.
[27]Yamamoto R,Aoki T,Koseki H,et al.A sphingosine-1-phosphate receptor type 1 agonist,ASP4058,suppresses intracranial aneurysm through promoting endothelial integrity and blocking macrophage transmigration[J].Br J Pharmacol,2017,174(13):2085.
[28]Galvani S,Sanson M,Blaho VA,et al.HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation[J].Sci Signal,2015,8(389):ra79.
[29]Zhang G,Yang L,Kim GS,et al.Critical role of sphingosine-1-phosphate receptor 2(S1PR2)in acute vascular inflammation[J].Blood,2013,122(3):443-455.
[30]Liu W,Liu B,Liu S,et al.Sphingosine-1-phosphate receptor 2 mediates endothelial cells dysfunction by PI3K-Akt pathway under high glucose condition[J].Eur J Pharmacol,2016,776:19-25.
[31]Zhang W,An J,Jawadi H,et al.Sphingosine-1-phosphate receptor-2 mediated NF-κB activation contributes to tumor necrosis factor-αinduced VCAM-1 and ICAM-1 expression in endothelial cells[J].Prostaglandins Other Lipid Mediat,2013,106:62-71.
[32]Wang F,Okamoto Y,Inoki I,et al.Sphingosine-1-phosphate receptor-2 deficiency leads to inhibition of macrophage proinflammatory activities and atherosclerosis in apo E-deficient mice[J].J Clin Invest,2010,120(11):3979-3995.
[33]T9lle M,Klockl L,Wiedon A,et al.Regulation of endothelial nitric oxide synthase activation in endothelial cells by S1P1 and S1P3[J].Biochem Biophys Res Commun,2016,476(4):627-634.
[34]Lin CC,Lee IT,Hsu CH,et al.Sphingosine-1-phosphate mediates ICAM-1-dependent monocyte adhesion through p38 MAPK and p42/p44 MAPK-dependent Akt activation[J].PLoS One,2015,10(3):e0118473.