HDL-mediated mechanisms of protection in cardiovascular disease

Low plasma levels of HDL-cholesterol (HDL-C) represent a strong and independent risk factor for cardiovascular disease. HDL particles display a wide spectrum of atheroprotective activities, which include effluxing cellular cholesterol, diminishing cellular death, decreasing vascular constriction, reducing inflammatory response, protecting from pathological oxidation, combating bacterial infection, lessening platelet activation, regulating gene expression by virtue of microRNAs, and improving glucose metabolism. It remains presently indeterminate as to whether some biological activities of HDL are more relevant for the protection of the endothelium from atherogenesis when compared with others. The multitude of such activities raises the question of a proper assay to assess HDL functionality ex vivo. Together with clear understanding of molecular mechanisms underlying atheroprotective properties of HDL, such assay will provide a basis to resolve the ultimate question of the HDL field to allow the development of efficient HDL-targeting therapies.