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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have