INCORPORATION OF CHOLESTEROL OXIDATION-PRODUCTS INTO CELL LIPIDS AND THEIR INFLUENCE ON THE PROLIFERATION OF CULTURED CARDIOMYOCYTES

We have investigated the incorporation of cholesterol oxidation produc ts into cardiomyocyte lipids and related this to changes in cell proli feration, evaluated by measuring cellular protein content. Primary cul tures of neonatal rat ventricular cells were supplemented with scalar concentrations of several cholesterol oxidation products (cholestan-5 alpha,6 alpha-epoxy-3 beta-ol, 5 alpha-cholestane-3 beta,5,6 beta-trio l, 5-cholesten-3 beta,4 beta-diol, 5-cholesten-3 beta-ol-7-one, and 5- cholesten-3-one). Although all the cholesterol oxidation products were incorporated into the cardiomyocyte lipids when added to the medium a t a concentration higher than 0.5 mu M, the extent of the incorporatio n of the different cholesterol oxidation products differed, depending on the concentration in the culture medium and on the chemical structu re of the compound. The effects of the cholesterol oxidation products on the cellular protein content were also different; 5 alpha-cholestan e-3 beta,5,6 beta-triol was shown to be the most potent inhibitor of c ell proliferation, followed by cholestan-5 alpha,6 alpha-epoxy-3 beta- ol, 5-cholesten-3 beta,4 beta-diol and 5-cholesten-3 beta-ol-7-one. 5- Cholesten-3-one did not affect the cellular protein content. The abili ty of cholesterol oxidation products to inhibit cell proliferation, an d their capacity to increase the permeability of the plasma membrane t o calcium, could be deleterious for cardiac cells.