Effects of clopidogrel on vascular proliferation and apoptosis in an atherosclerotic rabbit model

J Cardiovasc Pharmacol. 2010 Jun;55(6):617-24. doi: 10.1097/FJC.0b013e3181dc98dc.

Abstract

Inflammation, vascular proliferation. and apoptosis contribute to the process of atherosclerosis. Clopidogrel has been used to treat atherosclerosis; however, the mechanism is not entirely known. Compared with those of atorvastatin, we determined effects of clopidogrel on inflammatory factors, vascular proliferation, and apoptosis in an atherosclerosis rabbit model. New Zealand white rabbits were fed a normal diet or a high cholesterol diet for 7 weeks. The right iliac artery of animals except those in the negative control group were balloon-injured 1 week after initiation of the diet, and groups of animals were treated with clopidogrel (4 mg/kg per day), atorvastatin (2.5 mg/kg per day), or placebo (positive control group) for 6 weeks. We found that the placebo group had significant progression of atherosclerosis compared with the negative control group. In contrast, clopidogrel- or atorvastatin-treated rabbits showed a significant reduction in progression of atherosclerosis, including a low expression of high sensitivity C-reactive protein and platelet-derived growth factor, a reduced intima thickness, and reduced ratio of bcl-2/bax in the vascular wall. These results suggest that clopidogrel can retard the progression of established lesions that is related to inhibiting inflammation, cell proliferation, and promotion of cell apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / pathology
  • Atherosclerosis* / therapy
  • Atorvastatin
  • C-Reactive Protein / metabolism
  • C-Reactive Protein / pharmacology
  • C-Reactive Protein / therapeutic use
  • Catheterization
  • Clopidogrel
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Heptanoic Acids
  • Inflammation / drug therapy
  • Male
  • Platelet-Derived Growth Factor / pharmacology
  • Platelet-Derived Growth Factor / therapeutic use
  • Pyrroles
  • Rabbits
  • Random Allocation
  • Ticlopidine / analogs & derivatives
  • Tunica Intima / drug effects
  • Tunica Intima / metabolism
  • Tunica Intima / pathology

Substances

  • Heptanoic Acids
  • Platelet-Derived Growth Factor
  • Pyrroles
  • C-Reactive Protein
  • Atorvastatin
  • Clopidogrel
  • Ticlopidine