Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL: "Herniated" HDL, a common feature in diabetes

Scientific Reports
Núria AmigóXavier Correig

Abstract

Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin. We further characterized the HDL surface properties using atomic force microscopy and fluorescent probes to show an abnormal lipid distribution within smaller HDL particles, a subclass particularly enriched in the DM2 patients. The reduction in the size, force cholesterol esters and triglycerides to emerge from the HDL core to the surface, making the outer surface of HDL more hydrophobic. Interestingly, pharmacological interventions had no effect on this undesired configuration, which may expla...Continue Reading

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Citations

Oct 19, 2016·Free Radical Research·Julie M ProudfootTrevor A Mori
Feb 20, 2016·Molecular BioSystems·Laura A Filla, James L Edwards
Feb 28, 2020·Journal of the American Heart Association·Nuria AmigóSamia Mora
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Apr 17, 2020·Frontiers in Cardiovascular Medicine·Anne Jomard, Elena Osto
Jan 14, 2021·Journal of Structural Biology: X·Chris J MalajczukRicardo L Mancera

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Methods Mentioned

BETA
NMR
atomic force microscopy
AFM

Software Mentioned

NanoScope

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