title: 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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Yoon
authors.forename: Bong Jun
authors.initials: BJ
authors.lastname: Cho
authors.forename: Ho Seon
authors.initials: HS
authors.lastname: Park
authors.forename: Seon Mee
authors.initials: SM
authors.lastname: Kang
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Hak Chul
authors.initials: HC
authors.lastname: Jang
authors.forename: Hayley
authors.initials: H
authors.lastname: Shin
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Lee
authors.forename: Young Bum
authors.initials: YB
authors.lastname: Kim
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Soo
authors.initials: S
authors.lastname: Lim
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D014292:Trimetazidine / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D014665:Vasodilator Agents; D014292:Trimetazidine