Journal of Metabolic Syndrome

Desialylated Atherogenic Low-Density Lipoprotein in Atherosclerosis

Abstract

Alexander N. Orekhov

Pathogenesis of atherosclerosis and the search for novel therapies and diagnostic markers remain major problems of modern medicine. Currently available therapeutic approaches are often not sufficiently effective, probably due to the complexity of the disease mechanisms. This review focuses on the evaluation of low-density lipoprotein (LDL) as risk factor for atherosclerosis. We summarize the current paradigm of LDL involvement in atherogenesis. We question the currently widely accepted hypothesis of the central role of oxidized LDL in atherogenesis and present an alternative concept of multiple modifications of LDL that confers its pro-atherogenic properties. According to a series of studies conducted with blood serum and LDL from atherosclerotic patients, desialylation is one of the earliest if not the first atherogenic modification of LDL. Desialylation occurs in the bloodstream and is followed by a cascade of other modifications, including the reduction of LDL particle size and increase of its density, acquisition of negative electrical charge, oxidation, and formation of highly atherogenic complexes.