Attenuation of inflammation and expansive remodeling by Valsartan alone or in combination with Simvastatin in high-risk coronary atherosclerotic plaques.
OBJECTIVE
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.
Chatzizisis
Yiannis S
YS
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
Jonas
Michael
M
Beigel
Roy
R
Coskun
Ahmet U
AU
Baker
Aaron B
AB
Stone
Benjamin V
BV
Maynard
Charles
C
Gerrity
Ross G
RG
Daley
William
W
Edelman
Elazer R
ER
Feldman
Charles L
CL
Stone
Peter H
PH
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000473:pathology; D001794:Blood Pressure; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D007249:Inflammation; D008055:Lipids / Q000737:chemistry; D008297:Male; D011817:Rabbits; D012306:Risk; D019821:Simvastatin / Q000494:pharmacology*; D013314:Stress, Mechanical; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000959:Antihypertensive Agents; D008055:Lipids; D013777:Tetrazoles; D000068756:Valsartan; D019821:Simvastatin; D014633:Valine
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