摘要
高血压是一种复杂的临床疾病,发病机理非常复杂,涉及与动脉粥样硬化和血栓形成有关的多个基因和环境因素以及它们之间的相互作用。通常,富含脂质的动脉粥样硬化斑块的破裂是急性血栓形成的基础,是从动脉硬化性疾病的稳定期或亚临床期到急性心肌梗死、缺血发作和外周血栓形成的转变。迄今,对这些动脉血栓性疾病的预防很大程度上限于环境因素,但是有一半的血栓栓塞查不到这些危险因素,流行病学研究表明,环境因素不能完全解释血栓的形成。遗传因素在冠心病的发生发展过程中起重要作用。因此,当前的研究焦点已经从外界环境因素转移到了血栓形成和动脉粥样硬化的分子遗传学基础上,以进一步了解动脉血栓形成的病理机制。
越来越多的临床和实验证据表明,原发性高血压(Essential hypertension, EH)存在促凝高凝状态。先前的研究已经发现几个基因突变是促凝的危险因子,其中血栓调节蛋白(thrombomodulin,TM)基因、转化生长因子-β1(transforming growth factor-beta-1,TGF-β1)基因和白细胞介素-10(interleukin 10, IL-10)基因是非常重要的有潜力的候选基因。本研究旨在分别评价这三个基因多态性对高血压及其心血管并发症发生发展的影响。
1、可溶性血栓调节蛋白基因
可溶性血栓调节蛋白(Soluble thrombomodulin ,sTM)作为内皮损伤或内皮功能障碍的特殊血浆标志物可能与高血压并发症有关,并可能影响血压高低。我们选择高血压患者286例,高血压伴冠心病(coronary heart disease,CHD)患者113例和年龄性别相匹配的健康对照者213例,采用聚合酶链反应-限制性片段长度多态性(PCR–RFLP)分析方法检测TM -33G>A多态性,流式细胞分析技术检测TM在单核细胞表面的表达以及ELISA测定血浆sTM水平。结果单核细胞表面的TM水平在高血压患者尤其是高血压伴CVD患者中呈现低表达,并且与TM–33位点多态性相关。但sTM和TM–33位点A等位基因频率在高血压组和健康对照组之间以及在高血压组和CVD组之间无显著性差异。同样基因型分布在各组之间亦无显著性差异,GG基因型与GA+AA基因型之比在EH组为77%:23%;CVD组为79.7%:20.3%;对照组为81.2%:18.8%。(与对照组比较均P>0.05)。用高血压公认的危险因素(吸烟,饮酒,胆固醇)校正后,TM–33位点基因型分布和等位基因频率仍无显著性差异。结论TM -33G>A多态性似乎与汉族人群高血压及CHD发病无明显相关。TM基因多态性可能影响其在细胞表面的表达,细胞表面TM低表达可能是高血压CHD发病的危险因素,但这种表达差异可能在高血压发生发展过程中被其他因素的影响所掩盖。
2、转化生长因子-β1基因
流行病学、临床和试验研究提示转化生长因子-β1(transforming growth factor-beta-1,TGF-β1)可能在高血压的发病过程中起重要作用,TGF-β1是一种多潜能的生长因子,能够调节细胞的生长和分化,调节细胞外基质及其修复,从而进一步调节炎症和免疫应答,参与血管的修复,而这一过程与高血压血管和靶器官损害的发病有关。TGF-β1也可以通过刺激内皮素-1和/或肾上腺素的分泌调节血压。本研究旨在探讨循环水平的TGF-β1蛋白与血压的相关关系,以及TGF-β1基因多态性各等位基因及基因型在高血压病冠心病患者中的分布频率,分析其基因型和血清水平与高血压病冠心病的相关关系。方法采用序列特异性引物聚合酶链反应( PCR-SSP),检测286例高血压病患者、113例高血压冠心病患者及213名正常对照者TGF-β1基因+869T/C、+915G/C多态性,同时采用双抗体夹心ABC-ELISA法测定血清TGF-β1水平。结果高血压冠心病组血清TGF-β1水平显著高于高血压组和对照组,高血压组显著高于对照组,均P<0.05。TGF-β1基因+915G/C多态性在高血压组、冠心病组和正常人群中的分布差异均无统计学意义(均P>0.05) ,而TGF-β1+869T/C基因多态性在冠心病组和正常人群中的分布差异存在统计学意义(均P<0.05),等位基因频率的相对风险分析发现, C等位基因携带者患高血压病冠心病的风险是T等位基因的1.681倍(OR =1.681, 95% CI: 1.213～2.328),提示TGF-β1+869位点C等位基因可能是冠心病的危险因素之一。携带C等位基因的高血压冠心病患者血清TGF-β1水平显著高于不携带者,呈现CC基因型者TGF-β1水平显著高于TC基因型者,TC基因型者TGF-β1水平显著高于TT基因型者(CC:TC:TT为7.06±0.69: 6.84±0.75: 6.12±0.58。表明TGF-β1 +869T/C位点的等位基因仅有一个发生改变即可以影响其蛋白水平的表达,C等位基因是TGF-β1的高表达基因。
结论TGF-β1基因+ 869T/C多态性与高血压、冠心病的发病具有相关性,其中C等位基因可能是高血压、冠心病发病的遗传易感基因;携带C等位基因的个体可能通过促进TGF-β1的高度表达进而增加了高血压冠心病的发病风险,并且TGF-β1对冠心病的影响可能独立于血压水平之上,支持TGF-β1对冠心病的影响可能是通过细胞外基质的沉积而发挥作用的理论。而TGF-β1基因+915G/C多态性与高血压和冠心病的发病风险无显著关联。
3、白细胞介素-10基因
白介素-10(interleukin-10, IL-10)是由巨噬细胞、T细胞和B细胞产生的细胞因子,通过抑制促炎性细胞因子和B细胞的活性发挥抗炎作用,IL-10在人类动脉粥样硬化(Atherosclerosis, AS)的早期和进展中均有表达,并能抑制许多与动脉粥样硬化斑块形成、破裂和血栓形成有关的细胞进程。冠心病的病理基础是动脉粥样硬化和血栓形成。动脉粥样硬化的形成对损伤血管内膜而言既是免疫反应过程,又是炎性反应的过程。IL-10是主要的炎性调节因子,其分泌大约有75%由遗传因素决定,因此,IL-10基因可能与动脉粥样硬化及其并发症有关,是研究冠心病的一个有潜力的候选基因。本研究旨在探讨白细胞介素-10(IL-10)基因- 627位点多态性与早发冠心病和血清IL-10水平的相关关系。方法应用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)分析方法,检测早发冠心病(CHD)患者163例和正常对照者112例IL-10基因-627位点多态性,采用ELISA法检测血清IL-10水平。结果IL-10基因-627位点基因型和等位基因频率在冠心病组和对照组之间无显著性差异,χ2值分别为1.9324, 1.5703, P>0.05。按性别分层分析IL-10基因型和等位基因频率,男性组χ2值分别为1.2708,0.8595,P>0.05;女性组χ2值分别为0.8254, 0.7127, P>0.05。血清IL-10水平在AA型、AC型和CC型之间存在显著性差异, P<0.05,但在冠心病组和对照组之间无显著性差异, P>0.05。结论IL-10基因-627位点多态性与中国人汉族人冠心病的易感性无显著关联,并且,这种关系不受性别因素的影响。但IL-10基因-627 A/C多态性可能影响IL-10基因的转录活性。
Hypertension is a complex disorder that involves multiple genetic and environmental factors interacting to produce the characteristic phenotype. The pathogenesis of arterial thrombotic disease is very complex and involves multiple genetic and environmental factors related to atherosclerosis and thrombosis, as well as their interaction. Classically, acute thrombosis at the site of a ruptured, lipid-rich atherosclerotic plaque is understood as the precipitating event in the transition from stable or subclinical atherosclerotic disease to acute myocardial infarction (MI), ischemic stroke (IS), or peripheral arterial occlusion. To date, the prevention of arterial thrombotic disease has consisted of the modification of traditional cardiovascular risk factors that are largely environmental; however, approximately half of all thrombotic events occur in patients without such risk factors, and epidemiologic studies increasingly demonstrate that these are insufficient to explain completely the variations in incidence and risk.
Some studies have shown that inherited risk factors contribute significantly to the development of coronary artery disease (CAD). Thus, in the current era of elucidation of the human genome, investigators have focused on the molecular genetics of thrombosis and atherosclerosis to improve their understanding of the pathobiology of arterial thrombosis.
Increasing clinical and laboratory evidence suggests that hypertension per se may confer a prothrombotic or hypercoagulable state. Several genetic mutations affecting coagulation proteins have been suggested as prothrombotic risk factors. Among these genetic mutations, the thrombomodulin gene , transforming growth factor-beta-1 gene and interleukin 10 gene are an important potential candidate. This study aimed to estimate the proportion of incidence cardiovascular disease (CVD) among hypertensives that may be attributable to these gene polymorphisms.
1. Thrombomodulin (TM) gene
Soluble thrombomodulin (sTM) as abnormalities of levels of specific plasma markers of endothelial damage or dysfunction may be related to the complications of hypertension and the determination of blood pressure itself. We performed a case-control study, including 286 patients with essential hypertension(EH), 113 hypertensives with coronary arteries disease (CAD) and 213 age- and sex-matched controls. The TM -33G>A polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP) analysis. TM on monocytes was measured by flow cytometry and sTM was determined with ELISA . Results We found that hypertensives have lower thrombomodulin on monocytes especially in patients with CVD. But we did not find significant difference in the sTM and the frequency of the A allele between hypertensives with CVD (14.2%) and controls (11%, P=0.616;OR 1.106, CI 0.746～1.640), or hypertensives (12.1%) and controls ( P=0.244, OR 1.330, CI 0.877～7.153). Similarly, the difference of the genotypic distributions could be neglected across the groups: GG :(GA/AA) was 81.2%:18.8% in controls, 79.7%:20.3% in hypertensives with CVD, and 77%:23% in hypertensives, respectively (vs. controls, all P>0.05). The lack of association also persisted after adjusting for other conventional risk factors. Conclusions Our results suggested that lower TM on monocytes associated with CVD risk in hypertensives, but no association of sTM with blood pressure. It also seemed not to support a significant association of the TM -33G>A polymorphism with CVD and EH in Chinese Han population. TM gene mutation may have a mildly affects on TM expression that might be balanced out by other factors during the progress of hypertention.
2.Transforming growth factor-β1 (TGF-β1) gene
Epidemiologic, clinical, and experimental evidence has suggested that upregulation of transforming growth factor-β1 (TGF-β1) may play a role in hypertensive disease. TGF-β1 is a multifunctional cytokine that regulates cell growth and differentiation, modulation of extracellular matrix and repair, which in turn regulate inflammatory and immune responses and can be involved in vascular remodelling. Transforming growth factor-β1 has been implicated in the pathogenesis of the vascular and target organ complications of hypertension. TGF-β1 may also regulate blood pressure via stimulation of endothelin-1 and/or renin secretion. Herein we explored the hypothesis that circulating levels of TGF-β1 protein are correlates of blood pressure levels. And study the relationship of the allele frequencies and genotype distribution of TGF-β1 gene polymorphism in patients with essential hypertension and coronary artery disease, and to analyze a association of the serum levels and genotype of TGF-β1 with essential hypertension and coronary artery disease. Methods The polymorphisms of TGF-β1 gene , including polymorphisms of TGF-β1 gene +869T/C and +915G/C, were analyzed by sequence specific primers-polymerase chain reaction ( PCR-SSP) methods in 286 patients with essential hypertension ,113 coronary artery disease and 213 healthy controls, and the serum level of TGF-β1 was determined by enzyme-linked immunosorbent assay( ELISA). Results The patients with coronary artery disease group showed significantly higher serum levels of TGF-β1 than essential hypertensives and control group. And essential hypertensives group showed significantly higher serum levels of TGF-β1 than control group (all P<0.05) the distributions of TGF-β1 gene +915G/C polymorphism did not show significant differences among patients with coronary artery disease, essential hypertensives and control group (P>0.05), but the TGF-β1 gene +869T/C polymorphism was significantly different between coronary artery disease group and control group(P<0.05). The relative risk of suffering from coronary artery disease in carriers of the C allele was 1.681 times than carriers of the T allele (OR =1.681, 95% CI: 1.213～2.328). the serum level of TGF-β1 C allele carriers was significantly higher than nocarriers. the serum level of TGF-β1 CC genotype was higher than TC genotype, and the serum level of TGF-β1 TC genotype was higher than TT genotype(CC:TC:TT was 7.06±0.69: 6.84±0.75: 6.12±0.58. It is suggested that the C allele may affect the TGF-β1 expression,even only one changed C allele of TGF-β1 gene +869 may influence the serum level of TGF-β1 expression. Conclusions TGF-β1 gene +869T/C polymorphism was associated with coronary artery disease, and C allele may be a risk factor for coronary artery disease in which the TGF-β1 C allele may be a increased risk factor by enhancing the TGF-β1 expression in the pathogenesis of essential hypertension with coronary artery disease. But it seemed not to support a significant association of the TGF-β1 gene +915 G/C polymorphism with coronary artery disease.
3.Interleukin-10 gene
Interleukin-10 (IL-10) is a cytokine produced by macrophages, T cells and B cells. It exerts an anti-inflammatory activity by inhibiting the production of pro-inflammatory cytokines and by activating B cells. IL-10 is expressed in both early and advanced human atherosclerotic plaques and inhibits many cellular processes involved in plaque progression, rupture, or thrombosis. The basic pathology mechanisms of coronary heart disease is atherosclerotic plaques and thrombosis. Interleukin 10 (IL10) is a major immunoregulatory cytokine . About 75% of the variability in IL10 secretion is determined by genetic differences. Therefore IL-10 gene seems to be implicated in both atherosclerosis and its acute complications. the IL-10 gene appears to be a good candidate for coronary heart disease studies. So our study aimed to investigate the relationship between interleukin-10 gene–627 polymorphisms and Serum interleukin-10 production and earlier coronary heart disease (CHD). Methods The genotype and allele frequency of interleukin-10 -627 gene site was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). DNA samples were obtained from 163 patients with CHD and 112 controls. Serum IL-10 production was detected by ELISA method.
Results No significant difference was found in the distribution of IL-10 genotype and allele frequency between healthy controls and patients with CHD.χ2 values were 1.9324 , 1.5703 respectively. P>0.05.
Stratification analyses based on deferent sex, no significant difference was found in both male groups and female groups.χ2 values in male groups were 1.2708, 0.8595 and in female groups were 0.8254, 0.7127, respectively. P>0.05. Serum IL-10 production showed significant differences among AA genotype, AC genotype and CC genotype. But no significant difference was found between healthy controls and patients with CHD. Conclusions Our results suggest that IL-10–627 A/C polymorphisms are not associated with an increased risk of CHD, but it might have a role on IL-10 gene expression.
引文
[1] Abeyama K, Stern DM, Ito Y, Kawahara K, Yoshimoto Y, Tanaka M. The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism. J Clin Invest, 2005,115: 1267 ～1274.
[2] Amann K. Hypertrophy and hyperplasia of smooth muscle cells of small intramyocardial arteries in spontaneously hypertensive rats. Hypertension, 1995,25(1): 124 ～131.
[3] Anguera I, Miranda-Guardiola F, Bosch X, Filella X, Sitges M, Marin JL, Betriu A, Sanz G. Elevation of serum levels of the anti-inflammatory cytokine interleukin-10 and decreased risk of coronary events in patients with unstable angina. Am Heart J, 2002, 144(5): 811 ～817.
[4] Atabay B, Oren H, Irken G, Kizildag S, Tunali S, Turker M, Yilmaz S. Role of Transforming growth factor-[beta]1 gene polymorphism in childhood idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol, 2003, 25: 885 ～889.
[5] Boehme MW, Raeth U, Scherbaum WA, Galle PR, Stremmel W. Interaction of endothelial cells and neutrophils in vitro: k inetics of thrombomodulin, intercellular adhesion molecule-1 ( ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1): imp lications for the relevance as serological disease activity markers in vasculit ides. Clin Exp Immunol, 2000, 119: 250～254.
[6] Bartunek J, Weinberg EO, Tajima M, Rohrbach S, Katz SE, Douglas PS, Lorell BH. Chronic Ng-nitro-l-arginine methyl ester-induced hypertension. Circ, 2000, 101(4): 423 ～429.
[7] Berend I, Sara BH, Hurley K, et al. Tissue-restricted expression of thrombomodulin in the placenta rescues thrombomodulin-deficient mice from early lethality and reveals a secondary developmental block. Development, 2001, 128: 827～838.
[8] Blann AD, Farell A, Picton A, McCollum CN. Relationship between endothelial cell markers and arterial stenosis in peripheral and carotid artery disease. Thromb Res, 2000, 97(4): 209 ～216.
[9] Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: A marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol, 2003, 23: 168 ～175.
[10]Boivin GP, Molina JR, Ormsby I, Stemmermann G, Doetschman T. Gastric lesions in transforming growth factor beta-1 heterozygous mice. Lab Invest, 1996, 74(2): 513 ～518.
[11]Brooks WW, Conrad CH. Myocardial fibrosis in transforming growth factor beta(1)heterozygous mice. J Mol Cell Cardiol, 2000, 32(2): 187 ～95.
[12]Bouma BN, Marx PF, Mosnier LO, Meijers JC. Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U). Thromb Res, 2001, 101: 329 ～354.
[13]Buckova D, Izakovicva Holla L, Benes P, Znojil V, Vacha J. TGF-beta 1 gene polymorphisms. Allergy, 2001, 56: 1236 ～1237.
[14]Cambien F, Ricard S, Troesch A, Mallet C, Generenaz L, Evans A, Arveiler D, Luc G, Ruidavets JB, Poirier O. Polymorphism of the transforming growth factor-beta-1 gene in relation to myocardial infarction and blood pressure:The Etude Cas-Temoin de l’Infarctur du Myocarde(ECTIM) Study. Hypertension, 1996, 28: 881 ～887.
[15]Centrella M, Canalis E. Transforming and nontransforminggrowth factors are present in medium conditioned by fetalrat calvariae. Proc Natl Acad Sci USA, 1985, 82: 7335 ～9.
[16]Chalikias GK, Tziakas DN, Kaski JC, Hatzinikolaou EI, Stakos DA, Tentes IK, Kortsaris A, Hatseras DI. Interleukin-18: interleukin-10 ratio and in-hospital adverse events in patients with acute coronary syndrome. Atherosclerosis, 2005, 182(1): 135 ～143.
[17]Chao TH, Li YH, Chen JH, Wu HL, Shi GY, Tsai WC. Relation of Thrombomodulin Gene Polymorphisms to Acute Myocardial Infarction in Patients <50 Years of Age. Am J Cardiol,2004, 93: 204 ～207.
[18]Chatterjee S, Van Mar E. A word on the possible role of the circulating transforming growth factor beta-1 in hypertension, diabetes, obesity, smoking and human disease involving fibrosis. Med Sci Monit, 2005,11(9): LE10 ～11.
[19]Choi ME. Mechanism of transforming growth factor-β1 signaling: role of the mitogen activated protein kinases. ki dney Int, 2000, 58: S53 ～S58.
[20]Cicala C, Cirino G. Linkage between inflammation and coagulation: an update on the molecular basis of the crosstalk. Life Sci, 1998, 62(20): 1817 ～1824.
[21]Cone JB, Ferrer TJ, Wallace BH, Wang J, Hauer-Jensen M. Alterlations in endothelial thrombomodulin expression in zymosan-induced lung injury. Trauma, 2003, 54: 731 ～736.
[22]Conway EM, Van de Wouwer M, Pollefeyt S, Jurk K, Van Aken H, De Vriese A. The lectin-like domain of thrombomodulin confers by suppressing adhesin activated protein kinase pathways. J Exp Med,2002, 196: 565 ～577.
[23]Crilly A, Hamilton J, Clark CJ, Jardine A, Madhok R. Analysis of transforming growth factor β1 gene polymorphisms in patients with systemic sclerosis. Ann Rheum Dis, 2002, 61: 678 ～681.
[24]Dahlback B, Villoutreix BO. Regulation of blood coagulation by the protein C anticoagulant pathway: novel insights into structure-function relationships and molecular recognition. Arterioscler Thromb Vasc Biol, 2005, 25(7): 1311 ～1320.
[25]Daimon T, Nakano M. Immunohistochemical localization of thrombomodulin in the stratified epithelium of the rat is restricted to the keratinizing epidermis. Histochem Cell Biol, 1999, 112(6): 437 ～442.
[26]Derynck J E, Todaro GJ. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci USA, 1978, 75(8): 4001 ～4005.
[27]De Cristofaro R, De Candia E, Landolfi R. Effect of high- and low-molecular-weight heparins on thrombin-thrombomodulin interaction and protein C activation. Circulation,1998, 98(13): 1297 ～1301.
[28]De Vries JE. Immunosupressive and anti-inflammatory properties of interleukin-10. Ann Med 1995,27: 537 ～541.
[29]Donger C, Georges JL, Nicaud V, Morrison C, Evans A, Kee F, Arveiler D, Tiret L, Cambien F. New polymorphisms in the interleukin-10 gene-relationships to myocardial infarction. Eur J Clin Yamada Yamada Invest, 2001, 31: 9 ～14.
[30]El-Gamel A, Awad M, Sim E, Hasleton P, Yonan N, Egan J, Deiraniya A, Hutchinson IV. Transforming growth factor-beta-1 and lung allograft fibrosis. Eur J Cardiothorac Sur, 1998, 13: 424 ～430.
[31]Esmon CT, Owen WE. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. PNAS, 1981, 78(4): 2249～2252.
[32]Esmon CT, Esmon NL, Harris KW. Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation. J Biol Chem, 1981, 257: 7944 ～7947.
[33]Esmon CT, Owen WG. Identification of an endothelial cell cofactor for the thrombin-catalyed activation of proteinc. Proc Natl Acad Sci USA, 1981, 78: 527～ 528.
[34]Esmon CT. Thrombomodulin as a model of molecular mechanism that modulates protease specificity and function at the vessel surface. FASEB J, 1995, 9: 946 ～955.
[35]Esmon CT. Role of coagulation inhibitors in inflammation. Thromb Haemost, 2001, 86(1): 51-56.
[36]Fan BJ, Leung YF, Wang J, Lam SC, Liu Y, Tam QS. Genetic and environmental risk factors for primary open-angle glaucoma. Chin Med J, 2004, 117: 706 ～710.
[37]Faust SN, Heyderman RS, Levin M. Coagulation in severe sepsis: A central role for thrombomodulin and activated protein C. Crit Care Med, 2001, 29(sup1): S62 ～S67.
[38]Fedorak RN, Gangl A, Elson CO, Rutgeerts P, Schreiber S, Wild G. Recombinant Human Interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease. Gastroenterology, 2000, 119: 1473 ～1482.
[39]Fichtlscherer S, Breuer S, Heeschen C, Dimmeler S, Zeiher AM. Interleukin-10 serum levels and systemic endothelial vasoreactivity in patients with coronary artery disease. J Am Coll Cardiol. 2004,7, 44(1): 50-52.
[40]Fukuda N, HU WY, Kubo A, Endoh M, Kishioka H, Satoh C, Soma M, Izumi Y, Kanmatsuse K. Abnormal regulation of transforming growth factor-beta receptors on vascular smooth muscle cells from spontaneously hypertensive rats by angiotensin Ⅱ.Hypertension, 1998, 31(2): 672 ～ 677.
[41]Gonzalez W, Chen Z, Damon DH. Transforming growth factor-beta regulation of endothelin expression in rat vascular cell and organ cultures. J CardiovascPharmacol, 2001, 37(2): 219 ～226.
[42]Gerdts E, Papademetriou V, Palmieri V, Boman K, Bjornstad H, Wachtell K, Giles TD, Dahlof B, Devereux RB. Correlates of pulse pressure reduction during antihypertensive treatment in hypertensive patients with electrocardiographic LVH. Am J Cardiol, 2002, 89(4): 399 ～402.
[43]Girndt M, Kohler H. Interleukin-10 (IL-10): an update on its relevance for cardiovascular risk. Nephrol Dial Transplant, 2003, 18: 1976 ～1979.
[44]Glazer NL, Smith NL, Heckbert SR, Doggen CJ, Lemaitre RN, Psaty BM. Risk of Myocardial Infarction Attributable to Elevated Levels of Total Cholesterol Among Hypertensives. American Journal of Hypertension, 2005, 18: 759 ～766.
[45]Hahn AW, Ferracin F, Buhler FR , Pletscher A. Modulation of gene expression by high and low density lipoproteins in human vascularsmooth muscle cells. Biochem Biophys Res Commun, 1991, 178(3): 1465 ～1471.
[46]Hang LW, Hsia TC, Chen WC, Chen HY, Tsai JJ, Tsai FJ. Interleukin-10 gene –627 allele variants, not interleukin-1 beta gene and receptor antagonist gene polymorphsms, are associated with atopic bronchial asthma. J of clin lab anal, 2003, 17: 168 ～173.
[47]Hayward R, Nossuli TO, Scalia R, Lefer AM. Cardioprotective effect of interleukin-10 in murine myocardial ischaemia-reperfusion. Eur J Pharmacol, 1997, 334: 157 ～163.
[48]Healy AM, Rayburn HB , Rosenberg RD , Weiler H. Absence of the blood-clotting regulator thromboodulin causes embryonic lethality in mice before development of a functional cardiovascular system. Proc Nafl Acad Set U. S. A, 1995, 92: 850～854.
[49]Heeschen C, Dimmeler S, Hamm C W, Fichtlscherer S, Boersma E, Simoons ML, Zeiher AM; CAPTURE Study Investigators. CAPTURE Study Investigators. Serum level of the antiinflammatory cytokine interleukin-10 is an important prognosticdeterminant in patients with acute coronary syndromes. Circulation, 2003, 107(16): 2109 ～2114.
[50]Henke PK, DeBrunye LA, Strieter RM, Bromberg JS, Prince M, Kadell AM, Sarkar M, Londy F, Wakefield TW. Viral IL-10 gene transfer decreases inflammation and cell adhesion molecule expression in a rat model of venous thrombosis. J Immunol, 2000, 164: 2131 ～2141.
[51]Hess PJ, Seeger JM, Huber TS, Welborn MB, Martin TD, Harward TR. Exogenously administrated interleukin-10 decreases pulmonary neutrophil infiltration in a tumor necrosis factor-dependent murine model of acute visceral ischaemia. J Vasc Surg, 1997, 26: 113 ～118.
[52]Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Kajiyama G, Oshima T. Effects of ACEI imidapril on reactive hyperemia in patients with EH: relationship between treatment periods and resistance artery endothelial function. J Am Coll of Cardiol, 2001, 37(3): 863 ～870.
[53]Ireland H, Kunz G, Kyriakoulis K, Stubbs PJ, Lane DA. Thrombomodulin gene mutations associated with myocardial infarction. Circulation, 1997, 96: 15 ～18.
[54]Isermann B, Sood R , Pawlinski R , Zogg M, Kalloway S, Degen JL, Mackman N, Weiler H. The thrombomodulin-protoin C system is essential for the maintenance of pregnancy. Nat Med, 2003, 9(3): 331～337.
[55]Jackman RW, Beeler DL, Fritze L, Soff G, Rosenberg RD. Human thrombomodulin gene is intron depleted: nucleic acid sqquences of the cDNA and gene predict protein structure and suggest sites of regulatory control. Proc Natl Acad Sci,1987 ,84: 6425～6429.
[56]Jhingan A, Zhang L, Christiansen WT, Castellino FJ. The activities of recombinant gamma-carboxyglutamic-acid-deficient mutants of activated human protein C toward human coagulation factor Va and factor VIII in purified systems and in plasma. Biochemistry, 1994, 33(7): 1869 ～1875.
[57]Konstantoulas CJ, Cooper J, Warnock G, Miller GJ, Humphries SE, Irelanda H. A combination of two common thrombomodulin gene variants (-1208-1209TTdelTT andA455V) influence risk of coronary. Atherosclerosis 2004, 177: 97～104.
[58]Kagami S, Border WA,Miller DE, Noble NA. Angiotensin Ⅱstimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. J Cli n Invest, 1994, 93(6): 2431 ～2437.
[59]Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS. Production oftransforming growth factor beta by human T lymphocytesand its potential role in the regulation of T cell growth. J Exp Med, 1986, 163: 1037 ～1050.
[60]Kishida A , Nakashima M, Sakamoto N ,Serizawa T, Maruyama I, Akashi M. Study on complex formation between recombinant human thrombomodulin fragment and thrombin using surface plasmon resonance. Am J Hmtol, 2000, 63(3): 136～140.
[61]Kitani A, Fuss I, Nakamura K, Kumaki F, Usui T, Strober W. Transforming growth factor(TGF)- beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-beta1-mediated fibrosis. J Exp Med, 2003, 198(8): 1179 ～1188.
[62]Klahr S, Morrissey JJ. The role of vasoactive componnds, growth factor and cytokines in the progression of renal disease. Ki dney Int, 2000, 57: S7 ～S14.
[63]Kobayashi H, Sadakata H, Suzuki K, She MY, Shibata S, Terao T. Thrombomodulin release from umbilical endothelial cells initiated by preeclampsia plasma-induced neutrophil activation. Obstet Gynecol, 1998, 92(3): 425 ～430.
[64]Kube D, Rieth H, Eskdale J, Kremsner PG, Gallagher G. Structural characterization of the distal 5ˊflanking region of the human interleukin-10 gene. Genes Immun, 2001, 2: 181 ～190.
[65]Kullo IJ, Edwards WD, Schwartz RS. Vulnerable plaque: Pathobiology and clinical implications. Ann Intern Med, 2000, 129: 1050～1060.
[66]Kunz G, Ireland HA, Stubbs PJ, Kahan M, Coulton GC, Lane DA. Identification and characterization of a thrombomodulin gene mutation coding for an elongatedprotein with reduced expression in a kindred with myocardial infarction. Blood,2000, 95: 569 ～576.
[67]Kuroda K, awaguchi T, Skaletsky H, Brown LG, Minx PJ, Cordum HS, Waterston RH, Wilson RK, Silber S, Oates R, Rozen S, Page DC. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet, 2001, 29(3): 279 ～286.
[68]Langdahl BL, CarstensM, Stenkjaer L, Eriksen EF. Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis. Bone, 2003, 32: 297 ～310.
[69]Laviades C, Varo N, Diez J. Transforming growth factor-βin hypertensive with cardiorenal damadge. Hypertension, 2000, 36(5): 517 ～522.
[70]Lazarus R, Klimecki WT, Palmer LJ, Kwiatkowski DJ, Silverman EK, Brown A, Martinez F, Weiss ST. Single-Nucleotide polymorphisms in the interleukin-10 Gene: differences in frequencies, linkage disequilibrium patterns, and haplotypes in three United States ethnic groups. Genomics, 2002, 80: 223 ～228.
[71]Leask RL, Jain N, Butany J: Endothelium and valvular diseases of the heart. Microsc Res Tech, 2003, 60: 129 ～137.
[72]Le Flem L, Picard V, Emmerich J, Gandrille S, Fiessinger JN, Aiach M, Alhenc-Gelas M. Mutations in promoter region of thrombomodulin and venous thromboembolic disease. Arterioscler Thromb Vasc Biol, 1999, 19: 1098 ～1104.
[73]Lee L, Meyer TW, Pollock AS, Lovett DH. Endothelial cell injury initiates glomerular sclerosis in the rat remnant kidney. J Cli n Invest, 1995, 96: 953～964.
[74]Li JM, Brooks G. Differential portein expression and subcellular distribution of TGF beta 1, beta 2, beta 3 in cardiomyocytes during pressures overload induced hypertrophy. J Mol Cell Cardiol, 1997, 29(8): 2213 ～2224.
[75]Li B, Khanna A, Sharma V, Singh T, Suthanthiran M, August P. TGF-1 DNA polymorphisms, protein levels and blood pressure. Hypertension, 1999, 33: II-271 ～275.
[76]Li JJ, Guo YL, Yang YJ. Enhancing anti-inflammatory cytokine IL-10 may be beneficial for acute coronary syndrome. Med Hypotheses, 2005, 65(1): 103 ～106.
[77]Li JP, Wang XB, Chen CZ, Xu X, Hong XM, Xu XP, Xu X, Hong XM, Xu XP, Gao W, Huo Y. The association between paired basic amino acid cleaving enzyme 4 gene haplotype and diastolic blood pressure. Chin Med J, 2004, 117: 382 ～388.
[78]Lowe PR, Galley HF, Abdel-Fattah A, Webster NR. Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients. Crit Care Med, 2003, 31: 34 ～38.
[79]Lyon H, Lange C, Lake S, Silverman EK, Randolph AG, Kwiatkowski D, Raby BA, Lazarus R, Weiland KM, Laird N, Weiss ST. IL-10 gene polymorphisms are associated with asthma phenotypes in children. Genetic epidemiology, 2004, 26: 155 ～165.
[80]Majack RA. Beta-type transforming growth factor specifies organizational behavior in vascular smooth muscle cell cultures. J Cell Biol, 1987, 105: 465 ～471.
[81]Mallat Z, Besnard S, Duriez M, Deleuze V, Emmanuel F, Bureau MF, Soubrier F, Esposito B, Duez H, Fievet C, Staels B, Duverger N, Scherman D, Tedgui A. Protective role of interleukin210 in atherosclerosis. Circ Res, 1999, 85(8): el7 ～e24.
[82]Martin G, Duez H, Blanquart C, Berezowski V, Poulain P, Fruchart JC, Najib-Fruchart J, Glineur C, Staels B. Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I. J Clin Invest, 2001, 107: 1423 ～1432.
[83]Martinez-Gonzalez J, Alfon J, Berrozpe M, Badimon L. HMG-CoA reductase inhibitors reduce vascular monocyte chemotactic protein-expression in early lesions from hypercholesterolemic swine independently of their effect on plasma cholesterol levels. Atherosclerosis, 2001, 159: 27 ～33.
[84]Martinka P, Fielitz J, Patak A, Regitz-Zagrosek V, Persson PB, Stauss HM. Mechanisms of blood pressure variability-induced cardiac hypertrophy and dysfunction in mice with impaired baroreflex. Am J Physiol Regul Integr CompPhysiol, 2005, Mar, 288(3): R767 ～776.
[85]Massague J, Andres J, Attisano L, Cheifetz S, Lopez-Casillas F, Ohtsuki M, Wrana JL. TGF-beta receptors. Mol Reprod Dev, 1992, 32: 99 ～104.
[86]Massague J, Wotton D. Transcriptional control by the TGF beta/Smad signaling system. EMBO J, 2000, 19: 1745 ～1754.
[87]Matsushita Y, Yoshiie K, Imamura Y, Ogawa H, Imamura H, Takao S. A subcloned human esophageal squamous cell carcinoma cell line with low thrombomodulin expression showed increased invasiveness compared with a high thrombomodulin-expressing clone – thrombomodulin as a possible candidate for an adhesion molecule of squamous cell carcinoma. Cancer Lett,1998, 127: 195 ～201.
[88]McCachren SS, Diggs J, Weinberg JB, Dittman WA. Thrombomodulin expression by human blood monocytes and by human synovial tissue lining macrophages. Blood,1991, 78: 3128 ～3132.
[89]Mok CC, Lanchbury JS, Chan DW, Lau CS. Interleukin-10 promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus. Arthritis Rheum, 1998, 41: 1090 ～1095.
[90]Moore K, O’Garra A, De Waal Malefyt R, Vieira P, Mosmann TR. Interleukin-10. Ann Rev Immunol, 1993, 11: 165 ～190.
[91]Moore DF, Li H, Jeffries N, Wright V, Cooper RA, Elkahloun A, Gelderman MP, Zudaire E, Blevins G, Yu H, Goldin E, Baird AE. Using Peripheral Blood Mononuclear Cells to Determine a Gene Expression Profile of Acute Ischemic Stroke: A Pilot Investigation. Circulation,2005, 111: 212 ～221.
[92]Morise Z, Eppihimer M, Granger DN, Anderson DC, Grisham MB. Effects of lipopolysaccharide on endothelial cell adhesion molecule expression in interleukin-10 deficient mice. Inflammation, 1999, 23:99 ～110.
[93]Miller DL,Yaron R,Yellin MJ. CD40L-CD40 interactions regulate endothelial cell surface tissue factor and thrombomodulin expression. J Leukoc Biol, 1998, 63(3): 373 ～379.
[94]Nishihira K, Imamura T, Yamashita A, Hatakeyama K, Shibata Y, Nagatomo Y, DateH, Kita T, Eto T, Asada Y. Increased expression of interleukin-10 in unstable plaque obtained by directional coronary atherectomy. Eur Heart J, 2006, 27(14): 1685 ～1689.
[95]Norlund L, Holm J, Zoller B, Ohlin AK: A common thrombomodulin amino acid dimorphism is associated with myocardial infarction. Thromb Haemost, 1997, 77: 248 ～251.
[96]Ogawa H, Yonezawa S, Maruyama I, Matsushita Y, Tezuka Y, Toyoyama H. Expression of thrombomodulin in squamous cell carcinoma of the lung: its relationship to lymph node metastasis and prognosis of the patients. Cancer Lett,2000, 149: 95 ～103.
[97]Ohlin AK, Larsson K, Hansson M. Soluble thrombomodulin activity and soluble thrombomodulin antigen in plasma. J Thromb Haemost, 2005, 3: 976 ～982.
[98]Ohlin AK, Holm J, Hillarp A. Genetic variation in the human thrombomodulin promoter locus and prognosis after acute coronary syndrome. Thrombosis Research, 2004, 113: 319～326.
[99]Pérez Fernández R, Kaski JC. Interleukin-10 and Coronary Disease. Rev Esp Cardiol, 2002, 55(7): 738 ～750
[100]Quarmby S, Fakhoury H, Levine E, Barber J, Wylie J, Hajeer AH, West C, Stewart A, Magee B, Kumar S. Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients. Int J Radiat Biol, 2003, 79: 137 ～143.
[101]Rahn KH. Barenbrock M, Kosch M, Suwelack B, Witta J. Vessel wall alteratrons in patients With renal failure.Hypertens Res, 2000, 23(1): 3 ～6.
[102]Ruggeri Zm. Mechanisms initiating platelet thrombus formation. Thromb Haemost, 1997, 78(1): 611～614
[103]Rivera MA, Echegaray M, Rankinen T, Perusse L, Rice T, Gagnon J, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. TGF-1 gene-race interactions for resting and exercise blood pressure in the HERITAGE Family Study. J Appl Physiol, 2001, 9: 1808 ～1813.
[104]Roberts AB, Frolik CA, Anzano MA, Sporn MB. Transforminggrowth factors fromneoplastic and nonneoplastic tissues. Fed Proc, 1983, 42: 2621 ～2626.
[105]Rogy MA, Beinhauer Bg, Reinisch W, Huang L, Pokieser P Transfer of interleukin-4 and interleukin-10 in patients with severe inflammatory bowel disease of the rectum. Hum Gene Ther, 2000, 11: 1731 ～1741.
[106]Sadler JE: Thrombomodulin structure and function. Thromb Haemost,1997, 78(1): 392 ～395.
[107]Sakata Y, Masuyama T, Yamamoto K, Nishikawa N, Yamamoto H, Kondo H, Ono K, Otsu K, Kuzuya T, Miwa T, Takeda H, Miyamoto E, Hori M. Calcineurin inhibitor attenuates LVH, leading to prevention of heart failure in hypertensive rats. Circ, 2000, 102(18): 2269 ～2275.
[108]Salomaa V, Matei C, Aleksic N, Sansores-Garcia L, Folsom AR, Juneja H, Park E, Wu KK. Cross–sectional association of soluble thrombomodulin with mild peripheral artery disease. the ARIC study. Atherosclerosis, 2001, 157: 309 ～314.
[109]Salomaa V, Matei C, Aleksic N, Sansores-Garcia L, Folsom AR, Juneja H, Chambless LE, Wu KK. Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the ARIC study.a case-cohort study. Lancet, 1999, 355: 1729 ～1734.
[110]Smith DA, Irving SD, Sheldon J, et al. Serum levels of the antiinflammatory cytokine interleukin-10 are decreased in patients with unstable angina. Circulation, 2001, 104(7): 746 ～749.
[111]Sporn MB, Roberts AB, Wakefield LM, Assoian RK. Transforminggrowth factor-beta: biological function and chemicalstructure. Science, 1986, 233: 532 ～534.
[112]Sumiyoshi S, Nakashima Y, Chen YX, Itabe H, Sueishi K. Interleukin-10 expression is positively correlated with oxidized LDL deposition and inversely with T-lymphocyte infiltration in atherosclerotic intimas of human coronary arteries. Pathol Res Pract, 2006, 202(3): 141 ～150.
[113]Suthanthiran M, Li B, Song JO, Ding R, Sharma VK, Schwartz JE, August P. Transforming growth factor-βhyperexpression in African-American hypertensive, A novel mediator of hypertension and or target organ damage. Proc Natl Acad Sci,2000, 97(7): 3479～3484.
[114]Serne EH , Gans RO ,Maaten JC , Tangelder GJ, Donker AJ, Stehouwer CD. Impaired skin capillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction. Hypertension, 2001, 38(2) :238～242.
[115]Sawada K, Naiki M, Yago H, Matsushita K, Ohtsuki T, Kitagawa K, Matsumoto M, Hori M. Hypertension associated with reduced plasma thrombomodulin levels and a hypercoagulable state in rats. Clin Exp Hypertens, 2003, 25: 73～84.
[116]Takeshita S, Gal D, Leclerc G, Pickering JG, Riessen R, Weir L, Isner JM. Increased gene expression after liposome-mediated arterial gene transfer associated with intimal smooth muscle cell proliferation. In vitro and in vivo findings. J Clin Invest. 1994,93: 652～661.
[117]Taddei S, Ghiadoni L, Virdis A, Buralli S, Salvetti A. Vasodilation to bradykinin is mediated by an Quabain sensitive pathway as a compensatory mechanism for impaired nitric oxide availability in EH patients. Circ, 1999, 100(13): 1400～1405.
[118]Taddei S, Virdis A, Ghiadoni L, Salvetti G, Salvetti A. Endothelial dysfunction in hypertension. J Nephrol, 2000,13(3): 205～210.
[119]Taipale J, Saharinen J, Keski-Oja J. Extracellular matrixassociatedtransforming growth factor-beta: role in cancercell growth and invasion. Adv Cancer Res, 1998, 75: 87 ～134.
[120]Targonski PV, Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Lerman A. Coronary endothelial dysfunction is associated with an increased risk of cerebro-vascular events. Circulation, 2003, 107: 2805 ～2809.
[121]Tsiang M, Lentz SR, Sadler JE. Functional domains of membrane-bound human thrombomodulin: EGF-like domains four to six and the serine/threonine-rich domain are required for cofactor activity. J Biol Chem, 1992, 267: 6164 ～6170.
[122]Turner ST, Boerwinkle E. Genetic of hypertension, target-organ com-plications, and response to therapy. Circ, 2000, 102(20): 40 ～45.
[123]Tziakas DN, Chalikias GK, Antonoglou CO, Veletza S, Tentes IK, Kortsaris AX,Hatseras DI, Kaski JC. Apolipoprotein E genotype and circulating interleukin-10 levels in patients with stable and unstable coronary artery disease. J Am Coll Cardiol, 2006,48(12): 2471 ～2481.
[124]van Haelst PL, Tervaert JW, Bijzet J, Balje-Volkers C, May JF, Langeveld B, Gans RO. Circulating monocytes in patients with acute coronary syndromes lack sufficient interleukin-10 production after lipopolysaccharide stimulation. Clin Exp Immunol, 2004, 138(2): 364 ～368.
[125]Vaughan CJ, Gotto AM Jr, Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol, 2000, 35: 1 ～10.
[126]Wayne A, Border, Nancy A, et al. Interactions of transforming growth factor-βand angiotension Ⅱin renal fibrosis. Hypertension, 1998, 3(pt2): 181 ～ 188.
[127]Wells RG, Yankelev H, Lin HY, Lodish HF. Biosynthesis of thetype I and type II TGF-beta receptors. Implications forcomplex formation. J Biol Chem, 1997, 272: 11444 ～11451.
[128]Wen D, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE. Complete cDNA sequence and chromosome localization of the gene. Biochemistry,1987, 26: 4350 ～4357.
[129]Wu G, Chen YG, Ozdamar B, Gyuricza CA, Chong PA, Wrana JL, Massague J, Shi Y. Structural basis of Smad-recognition by the Smad anchor for receptor activation. Science, 2000, 287: 92 ～97.
[130]Wu KK, Aleksic N, Ballantyne CM, Ahn C, Juneja H, Boerwinkle E. Interaction between soluble thrombomodulin and intercellular adhesion molecule-1 in predicting risk of coronary heart disease. Circulation, 2003, 107: 1729 ～1732.
[131]Xu C, Lee S, Shu C, Masuda H, Zarins CK. Expression of TGF-β1 andβ3 but not apoptosis factors relates to flow-induced aortic enlargement. BMC Cardiovascular Disorders, 2002, 31, 2(1): 11.
[132]Yamada Y, Fujisawa M, Ando F, Niino N, Tanaka M, Shimokata H. Association of a polymorphism of the transforming growth factorbeta-1 gene with blood pressure in Japanese individuals. J Hum Genet, 2002, 47: 243 ～248.
[133]Yokata M, Ichihara S, Lin TL, Nakashima N, Yamada Y. Association of a T29 3 C polymorphism of the transforming growth factor-1 gene with genetic susceptibility to myocardial infarction in Japanese. Circulation, 2000, 101: 2783 ～2787.
[134]Zhai QH, Futrell N, Chen FJ. Gene expression of IL-10 in relationship to TNF-alpha, IL-1beta, and IL-2 in the rat brain following middle cerebral artery occlusion. J Neurol Sci,1997, 152: 119 ～124.
[135]Zhang LJ, Yu JP, Li D, Huang YH, Chen ZX, Wang XZ. Effects of cytokines on carbon tetrachloride induced hepatic fibrogenesis in rats. World J Gastroenterol, 2004, 10(1): 77 ～81.
[136]Zhao JG, Zhou XY, Huang JF, Chen JH, Gu DF. Association study of the thrombomodulin -33G>A polymorphism with coronary artery disease and myocardial infarction in Chinese Han population. Int J Cardiol,2005, 100: 383 ～388.
[137]ZuK-Popiolek L, Flak Z, Francuz T, Tendera M. Plasma endothelin-1 in patients with stable or unstable angina. Kardiol Pol, 2003, 58(6): 429 ～437.
[138]初少莉,朱鼎良,王谷亮,等. 细胞因子及相关受体基因位点与中国人群原发性高血压的连锁分析. 中华医学遗传学杂志, 2002, 19(3): 221 ～224.
[139]廖新学,李欣.冠心病患者血浆血栓调节蛋白水平的测定及其临床意义.中国心血管病杂志, 2003, 8(2): 103 ～104.
[140]卢兴国, 付国胜, 黄连生, 等. 原发性高血压血浆血栓调节蛋白的水平及其临床意义. 上海医学检验杂志, 1999, 14(5): 304～ 305
[141]马国添,朱立光,吴波, 等. 冠心病患者血清γ干扰素、白细胞介素-10 的变化及其与血脂、血糖的关系. 广西医科大学学报,2004,21: 44 ～46.
[142]钱高潮 郑佐娅 殷兆芳 康文英 王从珠 王红 李稻 王鸿利. 冠心病TM1418位单核苷酸多态性研究, 中华血液学杂志, 2003, 24(9): 497 ～499.
[143]孙巧玲, 李定国, 胡良凯, 孙 超, 汪保灿, 陈源文. AdIL-10对肝星状细胞α-SMA、TGF-β1及TNF-α表达的影响. 胃肠病学和肝病学杂志, 2006, 15(2): 100 ～105.
[144]王涤非, 刘国良, 吴桂萍, 等.冠心病患者血浆血栓调节蛋白水平的测定.中国公共卫生, 1999, 15 (6): 527-528.
[145]夏春芳,霍勇,吴娜琼. 大鼠主动脉球囊损伤后白细胞介素10 的表达. 中国介入心脏病学杂志, 2001, 9(4): 712～714.
[146]盛西陵,王东明. 白介素10与冠心病、PTCA术后再狭窄. 实用临床医学, 2002, 3: 152 ～1154.
