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

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.

• Authors: Yiannis S Chatzizisis, Michael Jonas, Roy Beigel, Ahmet U Coskun, Aaron B Baker, Benjamin V Stone, Charles Maynard, Ross G Gerrity, William Daley, Elazer R Edelman, Charles L Feldman, Peter H Stone
• Journal: Atherosclerosis (Atherosclerosis) Vol. 203 Issue 2 Pg. 387-94 (Apr 2009) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 18786669 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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