New frontiers in atherosclerosis prevention and treatment: HDL as a novel therapeutic target

Abstract

The high-density lipoprotein (HDL) system offers an attractive target for novel therapeutic approaches to prevent or treat atherosclerosis. Clinical preventative studies with HDL modulators, both increasing HDL levels [peroxisome proliferator activator receptor (PPAR) α agonists] and stimulating turnover [cholesteryl ester transfer protein (CETP) activators] have led to favorable outcomes. Treatment of preexisting atherosclerosis with novel HDL mimetics, i.e., wild-type recombinant apo A-I, reconstituted HDL from human serum, large unilamellar phospholipid vesicles (LUV), and the recombinant apo A-I Milano dimer (AIM) offer exciting opportunities. Recent findings with AIM are consistent with the hypothesis that direct HDL administration can rapidly regress coronary plaques.