Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL: "Herniated" HDL, a common feature in diabetes
Por:
Amigo, N, Mallol, R, Heras, M, Martinez-Hervas, S, Vaca, FB, Escola-Gil, JC, Plana, N, Yanes, O, Masana, L, Correig, X
Publicada:
18 ene 2016
Resumen:
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 explain the lack of clinical benefits in DM2 subjects.
Filiaciones:
Amigo, N:
Univ Rovira & Virgili, IISPV, Dept Elect Engn, Metabol Platform, E-43007 Tarragona, Spain
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Mallol, R:
Univ Rovira & Virgili, IISPV, Dept Elect Engn, Metabol Platform, E-43007 Tarragona, Spain
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Heras, M:
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Univ Rovira & Virgili, St Joan Univ Hosp, Res Unit Lipids & Atherosclerosis, Vasc Med & Metab Unit,IISPV, E-43201 Reus, Spain
Martinez-Hervas, S:
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Univ Valencia, Hosp Clin Univ, INCLIVA, Endocrinol & Nutr Dept,Dept Med, Valencia 46010, Spain
Vaca, FB:
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Inst Invest Biomed IIB St Pau, Barcelona 08025, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Bellaterra 08193, Spain
Escola-Gil, JC:
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Inst Invest Biomed IIB St Pau, Barcelona 08025, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Bellaterra 08193, Spain
Plana, N:
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Univ Rovira & Virgili, St Joan Univ Hosp, Res Unit Lipids & Atherosclerosis, Vasc Med & Metab Unit,IISPV, E-43201 Reus, Spain
Yanes, O:
Univ Rovira & Virgili, IISPV, Dept Elect Engn, Metabol Platform, E-43007 Tarragona, Spain
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Masana, L:
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Univ Rovira & Virgili, St Joan Univ Hosp, Res Unit Lipids & Atherosclerosis, Vasc Med & Metab Unit,IISPV, E-43201 Reus, Spain
Correig, X:
Univ Rovira & Virgili, IISPV, Dept Elect Engn, Metabol Platform, E-43007 Tarragona, Spain
Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid 28029, Spain
Gold, Green Published
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