Effect of Tissue Hypoxia on the Development of Atherosclerosis

Abstract

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.

From these results, we conclude that under the hyperlipidemic condition, cell hypoxia plays an important role in atherogenesis. The hypothetical mechanisms of hypoxia on the development of atherosclerosis are proposed.