HDL e aterosclerosi: ruolo delle modificazioni di apoA-1

High-density lipoprotein (HDL) protects against atherosclerosis through multiple mechanisms that include amelioration of endothelial dysfunction, antioxidative, anti-inflammatory and antiapoptotic effects and removal of cholesterol excess from macrophages. Under particular circumstances, HDL loses its atheroprotective properties, resulting in the formation of dysfunctional HDL particles. Dysfunctional HDL particles increase proinflammatory signaling and reduce reverse cholesterol transport (RCT). Epidemiological studies have demonstrated that plasma HDL levels independently predict the risk of developing atherosclerosis and cardiovascular disease. More recently, however, it has emerged that HDL quality also seems to be an important parameter in atheroprotection and the HDL can be functionally deficient in populations at high risk of cardiovascular disease (CHD). Apolipoprotein AI (apoA-I), the main protein of HDL, plays a crucial part in the first RCT step by enhancing sterol efflux from macrophages. Myeloperoxidase-mediated oxidation of Tyr (tyrosine) and Met (methionine) residues in apoA-I can damaged this apoprotein and drastically impairs the protein’s ability to promote cholesterol efflux via the ABCA1 pathway. The post-traslation modifications creates a dysfunctional HDL particles that are associated with an increased incidence of cardiovascular events. It’s important to evaluate the quality and not just the quantity of HDL when considering the risk of cardiovascular events because HDL cholesterol levels do not predict the composition and/or function of this lipoproteins. Levels of MetO (methionine sulfoxide) residues in plasma apoA-I, measured using an accurate, specific method, should be investigated and considered in prospective future studies in order to assess their possible role as a novel risk factor.