Simvastatin suppresses apoptosis in vulnerable atherosclerotic plaques through regulating the expression of p(53), Bcl-2 and Bcl-xL.
OBJECTIVE
Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has antioxidant and anti-inflammatory properties that are independent of lipid-lowering abilities. This experiment was carried out to explore the effects of simvastatin on apoptosis in vulnerable atherosclerotic plaques of apoE-deficient mice.


RESULTS
Eight weeks-old apoE(-/-) mice were fed a Western-type diet. Vulnerable atherosclerotic lesions were formed in the branchiocephalic artery at the age of 30-weeks, before simvastatin administration for 8 weeks. Simvastatin did neither affect the levels of plasma glucose and lipids, nor the size of atherosclerotic lesions. Analysis of plaque composition showed that simvastatin decreased the area of lipid core and increased the amounts of macrophages and smooth muscle cells in atherosclerotic plaques of apoE(-/-) mice. In addition, simvastatin down-regulated the expression of vascular cell adhesion molecule-1 (VCAM-1) by both inhibition of nuclear factor kappa B (NF-кB) activation and suppression of the expression of the receptor for advanced glycation end products (RAGE). Moreover, we found that simvastatin administration led to reduced TUNEL-positive cells in the aortic root lesions, accompanied by up-regulation of Bcl-2 and Bcl-xL expression, and decreased P(53) expression as shown by Western blot.


CONCLUSIONS
In the present study, we show novel data to suggest that simvastatin could suppress apoptosis in vulnerable atherosclerotic plaques of apoE(-/-) mice by regulating the expression of apoptosis-related proteins, such as p(53), Bcl-2 and Bcl-xL.
The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
Weiwei
W
Qin
Yonggang
Y
Lu
Chengyan
C
Zhan
Tao
T
Shen
Lin
L
Dou
Yong
Y
Man
Shu
S
Wang
Chuanshi
C
Xiao
Yunfei
Y
Bian
Jian
J
Li
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001786:Blood Glucose / Q000032:analysis; D016122:Brachiocephalic Trunk / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D001057:Apolipoproteins E; C494813:Bcl2l1 protein, rat; D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D019821:Simvastatin