Transendothelial Transport of Low-Density Lipoproteins in Atherosclerosis: Mechanisms of Activation and Possible Therapeutic Targets

Despite advances in the prevention of cardiovascular events in recent decades, the risk of developing atherosclerosis and its complications remains a major challenge. One promising way to reduce this risk is to develop measures to inhibit the activated transport of low-density lipoproteins (LDLs) through the endothelium, which is the initial stage of atherosclerosis. Recent research has provided some molecular details of the mechanism, including the roles of caveolin-1, LDL receptors, and certain motor proteins. This review summarizes data on recent advances in studying of LDL endothelial transcytosis, focusing on its role in atherogenesis as well as on its regulation by hemodynamics, lipoproteins, cytokines, and metabolic factors. Data on potential targets for inhibiting transendothelial LDL transport are also presented. A better understanding of the mechanisms of endothelial LDL transcytosis and the development of drugs to inhibit it may lead to improved treatment of atherosclerosis and more effective prevention of cardiovascular events.