In vitro models of anti-atherosclerotic effects of cardiovascular drugs.

In studies performed on cells isolated from the subendothelial intimal layer of both normal and atherosclerotic human aortas, cells from atherosclerotic lesions retained atherosclerotic properties while in primary culture, including enhanced proliferative activity and high lipid level. The content and composition of lipids in cultured cells remained unchanged for the first 10 to 12 days in culture and corresponded to the respective indices in freshly isolated cells. When added to an atherosclerotic cell culture, the calcium antagonist verapamil reduced the total intracellular cholesterol level by threefold and inhibited proliferation and collagen synthesis by cultured cells within 48 hours. Of the 12 calcium antagonists tested, verapamil and nifedipine demonstrated the greatest antiatherosclerotic activity. In contrast, nitrates had no effect on atherosclerotic parameters, while beta blockers increased atherosclerotic manifestations of cultured cells. In studies in which plasma was added to cell cultures, 2 to 4 hours after patients received oral nifedipine or verapamil, their plasma prompted antiatherosclerotic responses from cell cultures by reduced intracellular cholesterol and inhibited atherosclerotic cell proliferation. Plasma of patients who received oral propranolol, however, demonstrated atherogenic characteristics. The atherogenic properties of propranolol were inhibited by nitroglycerin and nifedipine. Use of the atherosclerotic cell model allows the examination of the atherogenic and antiatherogenic properties of various drugs, thus possibly optimizing antiatherosclerotic therapy.