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《国际心血管病杂志》[ISSN:1006-6977/CN:61-1281/TN]

期数:

2020年03期

页码:

168-172

栏目:

基础研究

出版日期:

2020-06-08

文章信息/Info

Title:

The role of Src in oxidized low-density lipoprotein induced phenotypic switching of vascular smooth muscle cells

作者:

李森 杨克 王艳萍 李海清 刘震杰 王坚 高志伟 潘以锋 何敏志 陈兵

310000 杭州,浙江大学医学院附属第二医院血管外科(李森,刘震杰,王坚,高志伟,潘以锋,何敏志,陈兵); 200025 上海交通

Author(s):

LI Sen¹;  YANG Ke²;  WANG Yanping²;  LI Haiqing²;  LIU Zhenjie¹;  WANG Jian¹;  GAO Zhiwei¹;  PAN Yifeng¹;  HE Minzhi¹;  CHEN Bin¹

1.Department of Vascular Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang 310000; 2. Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

关键词:

动脉粥样硬化;  氧化型低密度脂蛋白;  平滑肌细胞;  Src;  表型

Keywords:

Atherosclerosis;  Oxidized low-density lipoprotein;  Smooth muscle cells;  Src;  Phenotype

分类号:

-

DOI:

10.3969/j.issn.1673-6583.2020.03.010

文献标识码:

-

摘要:

目的:探究Src对氧化型低密度脂蛋白(oxLDL)诱导血管平滑肌细胞表型转化的调控作用。方法:体外培养小鼠原代平滑肌细胞,以不同浓度的oxLDL刺激血管原代平滑肌细胞,检测平滑肌细胞表型分子平滑肌细胞表型肌球蛋白重链11(MYH11)、巨噬细胞表型CD68的表达变化,以及Src的激活情况。通过小干扰RNA(siRNA)抑制Src蛋白表达,Src特异性抑制剂PP2抑制Src激活,观察Src对oxLDL诱导的平滑肌细胞表型转化的影响。结果:分别以0、12.5、25.0、50.0 μg/mL oxLDL刺激血管

Abstract:

Objective:To investigate whether Src can regulate oxidized low-density lipoprotein(oxLDL)induced phenotypic transformation of vascular smooth muscle cells(SMCs).Methods:The primary mouse SMCs were cultured in vitro. And then we stimulated SMCs with diffe

参考文献/References

[ 1 ] Matic LP, Rykaczewska U, Anton R, et al. Phenotypic modulation of smooth muscle cells in atherosclerosis is associated with downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM[J]. Arterioscler Thromb Vasc Biol, 2016, 36(9):1947-1961.
[ 2 ] Liu RJ, Lo L, Angelina JL, et al. ARHGAP18 protects against thoracic aortic aneurysm formation by mitigating the synthetic and proinflammatory smooth muscle cell phenotype[J]. Circ Res, 2017, 121(5):512-524.
[ 3 ] Kiyan Y, Tkachuk S, Hilfiker-Kleiner DA, et al. oxLDL induces inflammatory responses in vascular smooth muscle cells via urokinase receptor association with CD36 and TLR4[J]. J Mol Cell Cardiol, 2014, 66:72-82.
[ 4 ] Kumar A, Amteshwar SJ, Nirmal S. Pharmacology of Src family kinases and therapeutic implications of their modulators[J]. Fundam Clin Pharmacol, 2015, 29(2):115-130.
[ 5 ] Reinecke J, Caplan S. Endocytosis and the Src family of non-receptor tyrosine kinases[J]. Biomol Concepts, 2014, 5(2):143-155.
[ 6 ] Roskoski R. Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors[J]. Pharmacol Res, 2015, 94:9-25.
[ 7 ] Landon JI, Fowler AJ, Kimberly MP, et al. Dasatinib, a small molecule inhibitor of the Src kinase, reduces the growth and activates apoptosis in pre-neoplastic Barrett’s esophagus cell lines: evidence for a noninvasive treatment of high-grade dysplasia[J]. J Thorac Cardiovasc Surg, 2013, 145(2):531-538.
[ 8 ] Dupont L, Du L, Poulter M, et al. Src family kinase activity drives cytomegalovirus reactivation by recruiting MOZ histone acetyltransferase activity to the viral promoter[J]. J Biol Chem, 2019, 294(35):12901-12910.
[ 9 ] Ju XM, Jiao XM, Ertel A, et al. v-Src oncogene induces Trop2 proteolytic activation via cyclin D1[J]. Cancer Res, 2016, 76(22):6723-6734.
[10] Mei HJ, Ah-Rong N, Ji EP, et al. Resistance mechanism against trastuzumab in HER2-positive cancer cells and its negation by Src inhibition[J]. Mol Cancer Ther, 2017, 16(6):1145-1154.
[11] Sima A, Chiraz C, Kamel B, et al. Smooth muscle cell fate and plasticity in atherosclerosis[J]. Cardiovasc Res, 2018, 114(4):540-550.
[12] Osonoi Y, Mita T, Azuma K, et al. Defective autophagy in vascular smooth muscle cells enhances cell death and atherosclerosis[J]. Autophagy, 2018, 14(11):1991-2006.

备注/Memo

备注/Memo:

基金项目:国家自然科学基金面上项目(81470547); 浙江省自然科学基金(Q20H020047)
作者单位:310000 杭州,浙江大学医学院附属第二医院血管外科(李森,刘震杰,王坚,高志伟,潘以锋,何敏志,陈兵); 200025 上海交通大学医学院附属瑞金医院心脏科(杨克,王艳萍,李海清)
通信作者:陈兵,E-mail:2114008@zju.edu.cn

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更新日期/Last Update: 2020-06-08