High density lipoproteins and coronary heart disease. Future prospects in gene therapy.

Atherosclerosis cardiovascular disease is the leading cause of death in industrial societies. For coronary heart disease, hypercholesterolemia and dyslipoproteinemia are the major risk factors. Low serum levels of cholesterol in the HDL fraction is the most common abnormality found in patients with confirmed coronary artery disease. A therapeutical strategy consists in increasing the serum HDL cholesterol concentration in order to improve the 'reverse cholesterol transport'. Studies in transgenic mice and rabbits for human apo A-I or human lecithin cholesterol acyl-transferase showed that overexpression of these proteins increases serum HDL cholesterol concentration and reduces diet induced atherogenesis. Furthermore, adenovirus-mediated transfer of human apo A-I and LCAT genes in mice also increases circulating apo A-I and LCAT. Apo A-I and LCAT are two potential targets for gene therapy of patients with atherosclerosis associated with a low HDL cholesterol level.