mk-0524 and Arteriosclerosis

The high-density lipoproteins (HDLs) are produced by the liver and small intestine as well as on the surface of lipid-enriched macrophages in the subendothelial space of arterial walls. Unlike the apo B100-containing lipoproteins, the HDLs are uniquely antiatherogenic. Based on prospective observational studies performed throughout the world, there is a consistent inverse relationship between serum levels of HDLs and risk for cardiovascular events: low levels of high-density lipoprotein-cholesterol (HDL-C) are associated with increased risk, whereas high levels are usually associated with reduced risk for myocardial infarction, ischemic stroke, and cardiovascular mortality. Post hoc analyses of a number of studies using statins and fibrates have shown that raising serum HDL-C correlates with a reduction in risk for cardiovascular morbidity and mortality. Given these observations, enormous resources are being committed to the development of novel means by which to pharmacologically increase rates of HDL biosynthesis, modulate the functionality of HDL, and to promote reverse cholesterol transport with intravenous infusions of HDL particles.

Topics: Animals; Arteriosclerosis; Cholesterol Ester Transfer Proteins; Cholesterol, HDL; Humans; Hypolipidemic Agents; Indoles; Lipid Metabolism; Risk Assessment; Risk Factors