期刊
CARDIOVASCULAR DRUGS AND THERAPY
卷 33, 期 1, 页码 25-33出版社
SPRINGER
DOI: 10.1007/s10557-018-6844-4
关键词
Vascular smooth muscle cells; Tauroursodeoxycholic acid; Dedifferentiation; In-stent restenosis; Endoplasmic reticulum stress; IRE1; XBP1 signaling pathway
资金
- Co construction of Provincial Department key project [WKJ-ZJ-1729]
- Zhejiang Science and Technology Department Animal Experimental Research Project [2017C37141]
PurposeThe role of endoplasmic reticulum (ER) stress in cardiovascular disease is now recognized. Tauroursodeoxycholic acid (TUDCA) is known to have cardiovascular protective effects by decreasing ER stress. This study aimed to assess the ability of TUDCA to decrease ER stress, inhibit dedifferentiation of vascular smooth muscle cells (VSMCs), and reduce in-stent restenosis.MethodsThe effect of TUDCA on dedifferentiation of VSMCs and ER stress was investigated in vitro using wound-healing assays, MTT assays, and western blotting. For in vivo studies, 18 rabbits were fed an atherogenic diet to induce atheroma formation. Bare metal stents (BMS), BMS+TUDCA or Firebird stents were implanted in the left common carotid artery. Rabbits were euthanized after 28days and processed for scanning electron microscope (SEM), histological examination (HE), and immunohistochemistry.ResultsIn vitro TUDCA (10-1000mol/L) treatment significantly inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and migration in VSMCs in a concentration-dependent manner and decreased ER stress markers (IRE1, XBP1, KLF4, and GRP78). In vivo, we confirmed no significant difference in neointimal coverage on three stents surfaces; neointimal was significantly lower with BMS+TUDCA (1.60.2mm(2)) compared with Firebird (1.90 +/- 0.1mm(2)) and BMS (2.3 +/- 0.1mm(2)). Percent stenosis was lowest for BMS+TUDCA, then Firebird, and was significantly higher with BMS (28 +/- 4%, 35 +/- 7%, 40 +/- 1%; respectively; P<0.001). TUDCA treatment decreased ER stress in the BMS+TUDCA group compared with BMS.Conclusions TUDCA inhibited dedifferentiation of VSMCs by decreasing ER stress and reduced in-stent restenosis, possibly through downregulation of the IRE1/XBP1 signaling pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据