Atheroprotection with amlodipine: Cells to lesions and the PREVENT trial

Oxidized lipid and calcium regulatory abnormalities appear to play importan t roles in early atherogenesis secondary to cholesterol enrichment of the c ell membrane in endothelial and arterial smooth muscle cells (SMCs). Howeve r, the link between the two is poorly understood. The findings reviewed her e demonstrate that amlodipine has membrane-modifying and antioxidant action s at the cell membrane level in addition to its classical calcium channel b locking properties. These multiple pharmacologic actions may explain the ce llular mechanisms of the atheroprotective effects of amlodipine in spontane ous atherogenesis and in accelerated atherosclerotic syndromes. Recent anim al model studies have demonstrated that amlodipine inhibits the progression of atherosclerotic lesions and protects against restenosis after angioplas ty. Amlodipine inhibits the cholesterol-induced increase in calcium permeab ility in SMCs, and has been shown to repair abnormalities in SMC membrane s tructure. Recent data have also demonstrated that amlodipine has a marked a ntioxidant action in membrane bilayers enriched with polyunsaturated fatty acids. However, these findings have been in animal models only; the efficac y of amlodipine in atheroprotection in humans cannot be predicted. The PREV ENT trial has therefore been launched to examine the atheroprotective poten tial of amlodipine in spontaneous lesion development in humans with ischemi c heart disease and in the prevention of restenosis after angioplasty.