Mechanisms of atherosclerotic plaque stabilization for a lipophilic calcium antagonist amlodipine.
Coronary artery disease (CAD) is the result of atherosclerosis, a vascular disorder characterized by abnormalities in vasoconstriction and endothelial function, ultimately leading to partial or complete vessel occlusion. Because the atherosclerotic plaque is marked by changes in calcium regulation, there has been interest in a potential antiatherosclerotic role for calcium antagonists. In support of this hypothesis, a recent clinical study demonstrated in patients with CAD that treatment with the lipophilic dihydropyridine-type calcium antagonist amlodipine resulted in significantly fewer cardiovascular procedures and events. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) evaluated the effects of amlodipine on the development and progression of atherosclerotic lesions in coronary and carotid arteries in 825 patients with documented CAD. The results of PREVENT showed that patients receiving amlodipine had marked reductions in hospitalization for revascularization and unstable angina compared with placebo in a population consisting of either normotensive or controlled hypertensive patients. Ultrasound approaches determined that amlodipine therapy was also associated with significant slowing in carotid atherosclerosis-an important surrogate marker for CAD-over the 3-year period. This vascular-wall benefit associated with amlodipine treatment was not related to changes in blood pressure. The findings from PREVENT were consistent with a second reported study known as the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES). These clinical results have led to an interest in potential plaque-stabilization properties of this lipophilic calcium antagonist. In this article, cellular and molecular mechanisms of action that may contribute to a beneficial role for a calcium antagonist in the treatment of atherosclerosis will be reviewed.
Mason
R P
RP
Membrane Biophysics Laboratory, Division of Cardiology, Department of Medicine and Biochemistry, Medical College of Pennsylvania-Hahnemann University School of Medicine, Pittsburgh, Pennsylvania, USA. rpmason@elucidaresearch.com
D017311:Amlodipine / Q000378:metabolism* / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism
D002121:Calcium Channel Blockers; D017311:Amlodipine