The combined effect of inhibiting both ACAT and HMG-CoA reductase may directly induce atherosclerotic lesion regression

摘要: We hypothesized that coadministration of avasimibe and simvastatin would limit size, composition extent atherosclerotic lesions potentially promote lesion regression, since bioavailable ACAT inhibitors decrease monocyte-macrophage enrichment HMG-CoA reductase smooth muscle cell migration proliferation. Male New Zealand white rabbits were sequentially fed a 0.5% cholesterol, 3% peanut oil, coconut oil diet for 9 weeks chow-fat 6 prior to drug administration. A time zero control group was necropsied administration the progression various diets but untreated. Avasimibe (10 mg/kg), (2.5 mg/kg) or combination with administered in 8 weeks. Plasma total cholesterol exposure unchanged by reduced 21% both alone avasimibe. Combination decreased VLDL-cholesterol 56%. VLDL+IDL lipid similar simvastatin-treated animals. Administration cholesteryl ester fraction increased triglyceride comparable extents. Relative control, plus markedly thoracic aortic content coverage 50% arch size macrophage area 75 73%, respectively. With respect avasimibe+simvastatin 64% 73% when compared zero. Based on these data, we conclude despite changes plasma lipoprotein monotherapy, inhibition may not only directly blunt also regression pre-established lesions.