Nifedipine increases cholesteryl ester hydrolytic activity in lipid-laden rabbit arterial smooth muscle cells. A possible mechanism for its antiatherogenic effect.

TitleNifedipine increases cholesteryl ester hydrolytic activity in lipid-laden rabbit arterial smooth muscle cells. A possible mechanism for its antiatherogenic effect.
Publication TypeJournal Article
Year of Publication1985
AuthorsEtingin OR, Hajjar DP
JournalJ Clin Invest
Volume75
Issue5
Pagination1554-8
Date Published1985 May
ISSN0021-9738
KeywordsAnimals, Arteriosclerosis, beta-Galactosidase, Cattle, Cells, Cultured, Cholesterol, Cholesterol Esters, Cholesterol, Dietary, Female, Lysosomes, Muscle, Smooth, Vascular, Nifedipine, Rabbits, Sterol Esterase
Abstract

Calcium and cholesterol (CHOL) accumulation are characteristic features of human atherosclerotic plaques. Calcium channel blockers have been shown to increase calcium levels in myocardial cells and suppress free and esterified CHOL deposition in arteries of CHOL-fed animals. To test the hypothesis that Nifedipine alters CHOL metabolism, thereby decreasing free and esterified CHOL accumulation in smooth muscle cells (SMC), we cultured arterial SMC from rabbits fed a normal or egg-supplemented diet for 6 mo. Cultured cells were treated with 0.1 mg/liter Nifedipine every 3 d during a 1-wk experiment. Although Nifedipine significantly increased lysosomal and cytoplasmic cholesteryl ester (CE) hydrolase activity in normal SMC via increased levels of intracellular cyclic AMP, no change in total CHOL content was observed after 1 wk of Nifedipine treatment. Contrary to these observations, lipid-laden SMC demonstrated a significant 50% loss in CHOL and CE after treatment with Nifedipine, due in part to the observed increase in CE hydrolytic activities. These data support our hypothesis that Nifedipine decreases CHOL and CE accumulation in arterial SMC by increasing arterial CE hydrolysis.

DOI10.1172/JCI111860
Alternate JournalJ Clin Invest
PubMed ID3923040
PubMed Central IDPMC425495
Grant List5-TH, HL-074423 / HL / NHLBI NIH HHS / United States
HL-07423 / HL / NHLBI NIH HHS / United States
HL-18828 / HL / NHLBI NIH HHS / United States
Related Faculty: 
David P. Hajjar, Ph.D.

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