Effects of oxygenated derivatives of cholesterol on cholesterol uptake by cultured aortic smooth muscle cells
Peng, S.K.; Morin, R.J.; Tham, P.; Taylor, C.B.
Artery 13(3): 144-164
1985
ISSN/ISBN: 0098-6127 PMID: 4096649 Document Number: 247842
The cytotoxicity of oxygenated derivatives of cholesterol on the cultured cells may not only be due to their potent inhibition of cholesterol biosynthesis, but also could be related to their capability for inhibiting cholesterol uptake from exogenous sources, particularly in arterial cells, which synthesize cholesterol at a very slow rate. In cultured aortic smooth muscle cells, the most potent inhibitor of cholesterol uptake was cholestane-3.beta., 5.alpha., 6.beta. triol, which at 100 .mu.g/ml medium reduced uptake of cholesterol to 10% of the control. The next most potent inhibitors were 5.alpha.,6.alpha.- epoxycholesterol and 25-hydroxycholesterol, which reduced uptake of cholesterol to 60%. 7.alpha.- and 7.beta.-hydroxycholesterol and 7-ketocholesterol inhibited cholesterol uptake to 30-50%. A consequence of their inhibitory effects on cholesterol uptake could be a depletion of cell membrane cholesterol, resulting in alternations in membrane structure and function and eventually in cell death.