Effect of cerivastatin sodium, a new inhibitor of HMG-CoA reductase, on plasma lipid levels, progression of atherosclerosis, and the lesional composition in the plaques of WHHL rabbits

1 The aim of this study was to examine whether cerivastatin sodium, a new i nhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, affe cts the lesional composition of spontaneously developed atherosclerosis due to hypercholesterolaemia and delays progression of the lesions. 2 We administered cerivastatin to 2-month-old WHHL rabbits, a low-density l ipoprotein receptor-deficient animal model, at a dose of 0.6 mg kg(-1) day( -1) for 32 weeks. We examined the plasma lipid levels, the severity of athe rosclerosis, and composition of atherosclerotic lesions. Lesional compositi on was determined using immunohistostaining for macrophages and smooth musc le cells, and Azan-Mallory staining for collagen fibres and extracellular l ipid deposits. 3 Compared to the control group, the plasma cholesterol levels were decreas ed in the treated group by 39% (12.7+/-0.6 mmol L-1 versus 20.9+/-1.0 mmol L-1, P<0.001). Atherosclerosis was suppressed by about 37% as measured by t he thickness of the aortic lesions (158+/-13 mu m versus 250+/-15 mu m, P<0 .001), and by 28% as measured by coronary stenosis (62.7+/-11.4 versus 86.9 +/-12.2, P<0.05). In the cerivastatin group, regarding the per cent areas o f lesional components in the lesion area, the macrophages (21.0+/-1.5% vers us 27.9+/-1.9%, P<0.01) and extracellular lipid deposits (3.2+/-0.4% versus 5.1+/-0.4%, P<0.001) were decreased in the aortic lesions, and the per cen t area of macrophages in the coronary lesions was also decreased (4.9+/-1.4 % versus, 11.6+/-2.4%, P<0.05). The per cent area of smooth muscle cells an d collagen fibres did not significantly decrease. 4 These results indicate that cerivastatin contributed to the plaque stabil ization and delayed progression of early atherosclerosis in young WHHL rabb its, in addition to the potent hypolipidemic effects.