CALCIUM-CHANNEL BLOCKERS ENHANCE CHOLESTERYL ESTER HYDROLYSIS AND DECREASE TOTAL CHOLESTEROL ACCUMULATION IN HUMAN AORTIC TISSUE

被引:65
作者
ETINGIN, OR
HAJJAR, DP
机构
[1] CORNELL UNIV, MED CTR, COLL MED, DEPT PATHOL, NEW YORK, NY 10021 USA
[2] CORNELL UNIV, MED CTR, COLL MED, DEPT BIOCHEM, NEW YORK, NY 10021 USA
[3] CORNELL UNIV, MED CTR,COLL MED,NIH, SPECIALIZED CTR RES THROMBOSIS, NEW YORK, NY 10021 USA
关键词
atherosclerosis; calcium channel blockers; cholesterol metabolism; cyclic AMP;
D O I
10.1161/01.RES.66.1.185
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Calcium channel blockers (CCBs), which are used clinically for treatment of angina and hypertension, are known to inhibit calcium influx into arterial smooth muscle cells and thereby decrease smooth muscle cell contraction. In addition, they prevent cholesteryl ester (CE) accumulation, the hallmark of human atherosclerosis, in arteries of cholesterol-fed animals by cellular mechanisms that remain undefined. To assess whether CCBs enhance CE hydrolysis and reduce CE accumulation in human arterial cells, we measured activities of the CE metabolic cycle in aortic tissues that were stripped of endothelial cells and adventitia from 35 patients undergoing coronary artery bypass surgery. Patients who were treated with either nifedipine or diltiazem (n = 23) for several months demonstrated a threefold increase in arterial CE hydrolytic activities compared with untreated patients. This difference was independent of serum cholesterol levels, age, or treatment with other medications. No effects were observed on CE synthetic activity. Cyclic AMP levels in the aortic tissue of patients treated with CCBs were also significantly elevated twofold to threefold. In addition, both free and esterified cholesterol were significantly reduced in aortic tissue from patients taking CCBs compared with untreated patients. These data are the first to show that CCBs can increase CE hydrolysis in human aortic tissue by increasing intracellular cyclic AMP with resultant decrease in CE accumulation. Collectively, these findings support the hypothesis that CCBs can act as antiatherosclerotic agents in human tissue by mobilizing stored CE in the arterial wall.
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页码:185 / 190
页数:6
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