Effects of superoxide anion attack on the lipoprotein HDL

High-density lipoprotein (HDL) is an anti-atherosclerotic lipoprotein. Thanks to the activity of apolipoprotein ApoA1, the principal protein component of HDL, this last is responsible for converting cholesterol into ester form and transporting excessive cholesterol to the liver (reverse cholesterol transport RCT). When HDL undergoes oxidation, it becomes dysfunctional and proatherogenic. ApoA1 is a target of oxidation, and its alteration affects RCT and contributes to atherosclerosis development. Until now, the mechanism of HDL oxidation is not fully understood and only hydroxyl radicals seem to induce direct oxidation of protein and lipidic components of lipoproteins. Here we demonstrate that superoxide radical, widely produced in early atherosclerosis, directly oxidizes HDL, and as a consequence, ApoA1 undergoes structural alterations impairing its anti-atherosclerotic functions. Our results highlight in an in vitro system the potential mechanism by which O-2(Greek ano teleia-) triggers atherosclerotic pathogenesis in vivo. Our study gets the basis for therapeutic approaches focused on the management of superoxide generation in early atherosclerosis onset.

Automated summary

High-density lipoprotein (HDL) is an anti-atherosclerotic protein that converts cholesterol into ester form and transports excess cholesterol to the liver. However, when HDL undergoes oxidation, it becomes dysfunctional and contributes to the development of atherosclerosis. In this study, we found that superoxide radicals, produced during early atherosclerosis, directly oxidize HDL and impair the function of its protein component ApoA1. These findings provide insights into the potential mechanism of atherosclerosis development and suggest therapeutic approaches targeting superoxide generation.