Statin treatment remodels the HDL subclass lipidome and proteome in hypertriglyceridemia.

HDL particles vary in lipidome and proteome, which dictate their individual physicochemical properties, metabolism, and biological activities. HDL dysmetabolism in non-diabetic hypertriglyceridemia (HTG) involves subnormal HDL-cholesterol and apoAI levels. Metabolic anomalies may impact the qualitative features of both the HDL lipidome and proteome. Whether particle content of bioactive lipids and proteins may differentiate HDL subclasses (HDL2b, 2a, 3a, 3b and 3c) in HTG is unknown. Moreover, little is known of the effect of statin treatment on the proteolipidome of hypertriglyceridemic HDL and its subclasses. Non-diabetic, obese, HTG males (n=12) received pitavastatin calcium (4mg/day) for 180 days in a single-phase, unblinded study. ApoB-containing lipoproteins were normalized post-statin. Individual proteolipidomes of density-defined HDL subclasses were characterized pre- and post-statin. At baseline, dense HDL3c was distinguished by marked protein diversity and peak abundance of surface lysophospholipids, amphipathic DAG and dhCer, and core CE and TAG, (normalized to mol PC), whereas light HDL2b showed peak abundance of COH, SM, glycosphingolipids (MHC, DHC, THC and anionic GM3), thereby arguing for differential lipid transport and metabolism between subclasses. Post-statin, bioactive lysophospholipid (LPC, LPC(O), LPE and LPI) cargo was preferentially depleted in HDL3c. By contrast, baseline lipidomic profiles of ceramide, dhCer and related glycosphingolipids and GM3/PC were maintained across particle subclasses. All subclasses were depleted in TAG and DAG/PC. The abundance of apolipoproteins CI, CII, CIV and M diminished in the HDL proteome. Statin treatment principally impacts metabolic remodeling of the abnormal lipidome of HDL particle subclasses in non-diabetic HTG, with lesser effects on the proteome.

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare that they have no duality of interest.