Junichi Mukodani

Effects of hypoxia on sterol synthesis, acyl-CoA:cholesterol acyltransferase activity, and efflux of cholesterol in cultured rabbit skin fibroblasts.

To elucidate the mechanisms of cholesterol accumulation in cells under hypoxic conditions, we tested the effects of hypoxia on sterol synthesis, on the activity of acyl-CoA:cholesterol acyltransferase (ACAT), and on the efflux of cholesterol in cultured rabbit skin fibroblasts. Sterol synthesis was measured by the incorporation of 14C-acetate into sterol, and ACAT activity, by the incorporation of 14C-oleate into cholesteryl ester. Hypoxia suppressed both sterol synthesis and the efflux of cholesterol but increased ACAT activity. These results suggest that hypoxia disturbs the balance of cholesterol metabolism in cells and induces intracellular lipid accumulation.

Effect of Tissue Hypoxia on the Development of Atherosclerosis

It has been suggested that hypoxia enhances the development of atherosclerosis. The aim of this study was to clarify the mechanisms. Experiments were designed to observe the effects of hypoxic and hyperoxic inhalation in WHHL rabbits and have revealed that atherosclerotic lesions in the hypoxia group were larger than those in the hyperoxia group. Since there was no fluctuation in plasma cholesterol level, the effect of hypoxia was probably a direct one. Cell culture studies were carried out, using rabbit aortic smooth muscle cells and fibroblasts, and the cells were incubated in the medium supplemented with hyperlipidemic serum. The esterified cholesterol contents in the cells under the hypoxic condition were 2–3 times higher than those under control conditions. Analysis of cholesterol metabolism revealed that hypoxia increased ACAT activity and suppressed cholesterol efflux.