Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys

Department of Comparative Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1040, USA. kwilliams@cpm.bgsm.edu

OBJECTIVES: This study examined the direct effects of pravastatin on the artery wall of atherosclerotic monkeys after dietary lipid lowering. BACKGROUND: Clinical trials suggest that hepatic hydroxymethylglutaryl coenzyme A reductase inhibitors may reduce the risk of coronary heart disease out of proportion to their effect on angiographically assessed lumen stenosis. METHODS: Thirty-two cynomolgus monkeys were fed an atherogenic diet for 2 years (progression phase) and then fed a lipid-lowering diet either containing (n = 14) or not containing (n = 18) pravastatin in the diet for an additional 2 years (treatment phase). As designed, total plasma cholesterol and high density lipoprotein concentrations did not differ between groups at the beginning of or during the treatment phase of the experiment (p > 0.05). RESULTS: Quantitative angiography revealed that coronary arteries of the pravastatin-treated monkeys dilated 10 +/- 3%, whereas those from untreated control monkeys constricted -2 +/- 2% in response to acetylcholine (p < 0.05). There were no treatment effects on plaque size of coronary arteries measured at the end of the treatment phase of the study (0.110 +/- 0.048 mm2 [untreated] vs. 0.125 +/- 0.051 mm2 [pravastatin]; p > 0.05) or on the amount of reduction in plaque size in common iliac arteries during the treatment phase of the study (48 +/- 5% [untreated] vs. 45 +/- 6% [pravastatin]; p > 0.05). However, histochemical analysis of the atherosclerotic lesions indicated that the arteries from pravastatin-treated monkeys had significantly fewer macrophages in the intima and media, less calcification and less neovascularization in the intima (p < 0.05). CONCLUSIONS: We conclude that compared with control monkeys, the arteries of pravastatin-treated monkeys had better dilator function and plaque characteristics more consistent with plaque stability than those of monkeys not receiving pravastatin. These beneficial arterial effects of pravastatin occurred independently of plasma lipoprotein concentrations and despite similar changes in plaque size between the groups.

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