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Differential effects of trimetazidine on vascular smooth muscle cell and endothelial cell in response to carotid artery balloon injury in diabetic rats.

Abstract：

BACKGROUND:Treatment with trimetazidine (TMZ), 1-[2,3,4-trimethoxybenzyl] piperazine, dihydrochloride, improves cardiac function and ameliorates endothelial dysfunction. However, its potential efficacy against restenosis after balloon injury has not been addressed. We investigated the effect of TMZ on reducing the occurrence of restenosis in the carotid artery in response to balloon injury and explored potential mechanisms for the effects. MATERIAL AND METHODS:Streptozotocin (40 mg/kg)-injected Sprague-Dawley rats and Otsuka Long-Evans Tokushima Fatty rats were used for type 1 and type 2 diabetes models, respectively. Both types of rats were divided into three groups: control and TMZ treatment 10 and 20mg/kg per day (n=10 per group). TMZ or normal saline was given orally from 2 weeks before to 2 weeks after carotid injury. RESULTS:Four weeks of TMZ treatment resulted in a significant and dose-dependent reduction in the intima-media ratio in diabetic rats. This effect was accompanied by decreased proliferation of vascular smooth muscle cells (VSMCs) and accelerated re-endothelialization after carotid balloon injury. In vitro study with VSMCs decreased proliferation and migration, while human umbilical vein endothelial cells (HUVECs) increased proliferation and decreased apoptosis after TMZ treatment. Antioxidative effects of TMZ were observed in both VSMCs and HUVECs. CONCLUSIONS:Reduction of restenosis by TMZ treatment involved changes in antioxidative and anti-inflammatory properties, which are cell-specific effects on either survival or apoptosis. The specific actions and physiological effects of TMZ may contribute to better understanding of the pathogenesis of atherosclerosis, which is a major complication of diabetes mellitus.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Yoon JW,Cho BJ,Park HS,Kang SM,Choi SH,Jang HC,Shin H,Lee MJ,Kim YB,Park KS,Lim S

doi

10.1016/j.ijcard.2011.12.061

subject

Has Abstract

pub_date

2013-07-15 00:00:00

pages

126-33

issue

1

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(11)02242-X

journal_volume

167

pub_type

杂志文章

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