Primary culture of human aortic intima cells as a model for testing antiatherosclerotic drugs. Effects of cyclic AMP, prostaglandins, calcium antagonists, antioxidants, and lipid-lowering agents.
Smooth muscle cells isolated from atherosclerotic lesions of human aorta retain in primary culture their intrinsic in vivo characteristics: namely, enhanced proliferative activity and high lipid levels. We have tested the effect of different compounds on [3H]thymidine uptake and on the levels of phospholipids, triglycerides, cholesterol, and cholesteryl esters in cultured aortic cells. Effects, such as the inhibition of cellular proliferation and/or lowering of the intracellular lipid levels which would be regarded as antiatherosclerotic if exerted in vivo, were observed in vitro by the following compounds: dibutyryl cyclic AMP, cholera toxin, forskolin, methylisobutylxanthine, stable prostacyclin analogues, prostaglandins E2 and D2, verapamil, reserpine, alpha-tocopherol, butylated hydroxytoluene, lipostabil, and high density lipoproteins. In this paper, we discuss the possibility of using a primary culture of smooth muscle cells from an atherosclerotic human aorta for testing drugs for possible antiatherosclerotic activity.
D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001161:Arteriosclerosis / Q000188:drug therapy*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D050356:Lipid Metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology
D000975:Antioxidants; D011453:Prostaglandins; D003994:Bucladesine; D000242:Cyclic AMP; D002118:Calcium