Calcium Antagonists and Lipid-Lowering Agents in the Protection of the Arterial Wall

Abstract

Calcium antagonists (CAs) may affect major processes involved in the atheroma formation. Among the possible mechanisms CM modulate cholesteryl ester (CE) metabolism. We compared the effect of verapamil and nifedipine on cholesterol esterification in mouse peritoneal macrophages (MPM) in different conditions of Acyl-CoA: Cholesterol Acyltransferase (ACAT) activation. CE is formed in cells via ACAT, which senses free cholesterol (C) supplied by lysosomal hydrolysis of CE carried by lipoproteins. As expected, verapamil completely inhibited the ability of acetyl low-density lipoproteins (AcLDL) to stimulate cholesterol esterification when simultaneously incubated with these lipoproteins, but was less effective in cells previously loaded with cholesteryl esters or stimulated by 25hydroxycholesterol (25-0H). In the same experimental conditions, the results obtained with nifedipine indicate that this dihydropyridine has no major influence on cellular cholesterol esterification. However, the new dihydropyridine derivatives, lacidipine and elgodipine, very efficiently inhibited the ability of AcLDL and 25-0H to stimulate cholesterol esterification in MPM. It appears that CAs of different structure, even within the same class, may have various effects on esterification of cellular cholesterol.