Calcium antagonists and cholesteryl ester metabolism in macrophages.
Experimental data indicate that calcium antagonists modify cellular lipid metabolism in the arterial wall as part of their antiatherosclerotic action observed in animal models. In the present study, we investigated the effect of verapamil, nifedipine, and lacidipine (a new dihydropyridine derivative) on cholesteryl ester metabolism in cultured mouse peritoneal macrophages (MPMs). Cholesteryl esters are formed in the cell via acyl-CoA:cholesterol acyltransferase (ACAT), which senses free cholesterol supplied by lysosomal hydrolysis of lipoprotein cholesterol ester. Verapamil inhibited up to 99% the ability of acetyl-low-density lipoprotein (acLDL) to stimulate cholesterol esterification in macrophages, but was less effective in 25-hydroxycholesterol-stimulated MPMs and in cholesterol-loaded cells after acLDL removal. Cells incubated with [3H]cholesterol ester-acLDL and verapamil showed a reduction in the cholesterol/cholesteryl ester ratio. In the same experimental conditions, nifedipine displays minor or no effects on cholesterol esterification and in the cholesterol/cholesteryl ester ratio. On the contrary, the nifedipine-like lacidipine was active in inhibiting cholesterol esterification in macrophages elicited by acLDL. Our data indicate that calcium antagonists of different structure, even within the same class, may have various effects on cholesterol esterification in macrophages in culture.
Bernini
F
F
Institute of Pharmacological Sciences, University of Milan, Italy.
Bellosta
S
S
Didoni
G
G
Fumagalli
R
R
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000008:administration & dosage; D002788:Cholesterol Esters / Q000378:metabolism*; D006888:Hydroxycholesterols / Q000032:analysis; D008077:Lipoproteins, LDL / Q000032:analysis; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009543:Nifedipine / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D011374:Progesterone / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002788:Cholesterol Esters; D006888:Hydroxycholesterols; D008077:Lipoproteins, LDL; D011374:Progesterone; D002784:Cholesterol; D014700:Verapamil; D009543:Nifedipine