Simvastatin reduces expression and activity of lipoprotein-associated phospholipase A(2) in the aorta of hypercholesterolaemic atherosclerotic rabbits.
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) contributes to atherosclerotic plaque instability and subsequent sudden coronary death. Statins are associated with decreased stroke risk and may improve stability of atherosclerotic plaques. The present study investigated the effect of simvastatin on expression of Lp-PLA(2) levels in atherosclerotic plaques and on Lp-PLA(2) activity in atherosclerotic aortas. Rabbits were a fed chow (control group) or a high-cholesterol diet (atherosclerosis group) for 12 weeks. An additional group on the high-cholesterol diet received simvastatin (5 mg/kg per day) for the last 4 weeks (simvastatin group). Lp-PLA(2) activity in plasma and atherosclerotic aortas was significantly higher in the atherosclerosis group than in the control group and, consistent with this, abundant Lp-PLA(2) protein was detected in plaques in the atherosclerosis group. Simvastatin significantly reduced Lp-PLA(2) activity in plasma and aorta tissue, and reduced Lp-PLA(2) protein level in atherosclerotic plaques. Whereas there was no significant difference in total atherosclerotic lesion area between simvastatin and atherosclerosis groups, simvastatin significantly reduced macrophage content, lipid retention and the intima/media ratio but increased the content of smooth muscle cells in atherosclerotic lesions. Thus, statin treatment markedly reduced Lp-PLA(2) in both plasma and atherosclerotic plaques. This was associated with attenuation of the local inflammatory response and improved plaque stability.
Qiao
Z
Z
Department of Cardiology, Peking University People's Hospital, Beijing, China.
Ren
J
J
Chen
H
H
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005260:Female; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology
D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D019821:Simvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase