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.
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