Attenuation of inflammation and expansive remodeling by Valsartan alone or in combination with Simvastatin in high-risk coronary atherosclerotic plaques

Atherosclerosis. 2009 Apr;203(2):387-94. doi: 10.1016/j.atherosclerosis.2008.07.032. Epub 2008 Aug 5.

Abstract

Aims: We investigated the role of Valsartan (V) alone or in combination with Simvastatin (S) on coronary atherosclerosis and vascular remodeling, and tested the hypothesis that V or V/S attenuate the pro-inflammatory effect of low endothelial shear stress (ESS).

Methods: Twenty-four diabetic, hyperlipidemic swine were allocated into Early (n=12) and Late (n=12) groups. In each group animals were treated with Placebo (n=4), V (n=4) and V/S (n=4) and followed for 8 weeks in the Early group and 30 weeks in the Late group. Blood pressure, serum cholesterol and glucose were similar across the treatment subgroups. ESS was calculated in plaque-free subsegments of interest (n=109) in the Late group at week 23. Coronary arteries of this group were harvested at week 30, and the subsegments of interest were identified, and analyzed histopathologically.

Results: V alone or with S reduced the severity of inflammation in high-risk plaques. Both regimens attenuated the severity of enzymatic degradation of the arterial wall, reducing the severity of expansive remodeling. V alone or with S attenuated the pro-inflammatory effect of low ESS.

Conclusions: V alone or with S exerts a beneficial effect of reducing and stabilizing high-risk plaque characteristics independent of a blood pressure- and lipid-lowering effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Atherosclerosis / pathology
  • Blood Pressure
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / pathology*
  • Disease Models, Animal
  • Endothelium, Vascular / pathology
  • Inflammation*
  • Lipids / chemistry
  • Male
  • Rabbits
  • Risk
  • Simvastatin / pharmacology*
  • Stress, Mechanical
  • Tetrazoles / pharmacology*
  • Valine / analogs & derivatives*
  • Valine / pharmacology
  • Valsartan

Substances

  • Antihypertensive Agents
  • Lipids
  • Tetrazoles
  • Valsartan
  • Simvastatin
  • Valine