Plasma phospholipid transfer protein-mediated reactions are impaired by hypochlorite-modification of high density lipoprotein

Abstract

The two main functions of phospholipid transfer protein (PLTP) are the transfer of phospholipids between plasma lipoproteins and the conversion of high density lipoprotein (HDL), where preβ-HDL particles are generated. HDL is considered an anti-atherogenic lipoprotein due to its function in the reverse cholesterol transport, where preβ-HDL accepts cellular membrane cholesterol from peripheral tissues. However, the anti-atherogenic properties of native HDL may be abolished by oxidation/modification. Hypochlorous acid/hypochlorite (HOCl/OCl −)—a potent oxidant generated in vivo only by the myeloperoxidase–H 2O 2–chloride system of activated phagocytes—alters the physiological properties of HDL by generating a pro-atherogenic lipoprotein particle. Therefore, we have studied the effect of HOCl on the function of HDL subclass 3 (HDL 3) and triglyceride-enriched HDL 3 (TG-HDL 3) in PLTP-mediated processes in vitro. Modification of HDL 3 and TG-HDL 3 with increasing HOCl concentrations (oxidant:lipoprotein molar ratio between 25:1 and 200:1) decreased the capacity of the corresponding lipoprotein particles to accept phospholipids. Although binding of PLTP to unmodified and HOCl-modified lipoprotein particles was similar, the degree of PLTP-mediated HDL conversion was decreased upon HOCl oxidation. PLTP released apolipoprotein A-I (apoA-I) from HOCl-modified HDL 3, but the particles formed displayed no preβ-mobility. Based on these findings, we conclude that the substrate properties of HOCl-modified HDL 3 and TG-HDL 3 in PLTP-mediated processes are impaired, which indicates that the anti-atherogenic properties of HDL are impaired.