Pharmacological therapies for raising HDL cholesterol beyond synthetic small molecules.

Epidemiological studies support the hypothesis that HDL particles possess inherent atheroprotective properties. The protective properties of HDL are primarily attributed to its known involvement in cholesterol mobilization from peripheral tissues and reverse cholesterol transport for hepatic excretion of cholesterol; removal of excess cholesterol load from the arterial wall is essential for prevention or reversal of unstable plaque development. Other known protective properties of HDL include its anti-inflammatory, antioxidant, antithrombotic and vasoprotective activities, which have been demonstrated in preclinical models of disease. Pharmacological therapies aimed at increasing HDL are predicted to offer tremendous clinical benefit for the prevention and treatment of cardiovascular disease. Advances in biologicals as therapeutics provide new opportunities for drug discovery. This review discusses some of the potential benefits of therapeutic approaches designed to raise HDL beyond that of traditional synthetic small molecules.