CKD Increases Carbonylation of HDL and Is Associated with Impaired Antiaggregant Properties.

Autor:	Florens N; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France nans.florens@chu-lyon.fr.; Department of Nephrology, University Hospital of Lyon, E. Herriot Hospital, Lyon, France., Calzada C; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France., Lemoine S; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France.; Department of Nephrology, University Hospital of Lyon, E. Herriot Hospital, Lyon, France., Boulet MM; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France., Guillot N; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France., Barba C; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France., Roux J; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France., Delolme F; Protein Science Facility, SFR BioSciences, Centre National de la Recherche Scientifique (CNRS) UMS3444, INSERM US8, Claude Bernard University Lyon 1, École Normale Supérieure de Lyon (ENS de Lyon), Lyon, France., Page A; Protein Science Facility, SFR BioSciences, Centre National de la Recherche Scientifique (CNRS) UMS3444, INSERM US8, Claude Bernard University Lyon 1, École Normale Supérieure de Lyon (ENS de Lyon), Lyon, France., Poux JM; Association Pour l'Utilisation du Rein Artificiel dans la Région Lyonnaise (AURAL), Lyon, France., Laville M; Association Pour l'Utilisation du Rein Artificiel dans la Région Lyonnaise (AURAL), Lyon, France., Moulin P; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France.; Department of Endocrinology, University Hospital of Lyon, L. Pradel Hospital, Bron, France., Soulère L; Institute for Molecular and Supramolecular Chemistry and Biochemistry, University of Lyon, INSA-Lyon, UMR 5246 CNRS, Villeurbanne, France., Guebre-Egziabher F; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France.; Department of Nephrology, University Hospital of Lyon, E. Herriot Hospital, Lyon, France., Juillard L; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France.; Department of Nephrology, University Hospital of Lyon, E. Herriot Hospital, Lyon, France., Soulage CO; CarMeN Laboratory, University of Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1060, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), Claude Bernard University Lyon 1, Institut National de la Recherche Agronomique (INRA) U1397, Villeurbanne, France.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2020 Jul; Vol. 31 (7), pp. 1462-1477. Date of Electronic Publication: 2020 Jun 09.
DOI:	10.1681/ASN.2019111205
Abstrakt:	Background: CKD is associated with increased oxidative stress that correlates with occurrence of cardiovascular events. Modifications induced by increased oxidative stress particularly affect circulating lipoproteins such as HDL that exhibit antiatheromatous and antithrombotic properties in vitro . Methods: To explore the specific role of oxidative modifications of HDL in CKD and their effect on the platelet-targeting antiaggregant properties of HDL, we used a CKD (5/6 nephrectomy) rabbit model. For ex vivo assessment of the antiaggregant properties of HDL, we collected blood samples from 15 healthy volunteers, 25 patients on hemodialysis, and 20 on peritoneal dialysis. We analyzed malondialdehyde, 4-hydroxynonenal (HNE), and 4-hydroxy-2-hexenal protein adduct levels. Platelet aggregation and activation were assessed by aggregometry, thromboxane B2 assay, or FACS. We modified HDL from controls by incubating it overnight at 37°C with 100 µ M of HNE. Results: HDL from CKD rabbits and patients on hemodialysis had HNE adducts. The percentage of platelet aggregation or activation induced by collagen was significantly higher when platelets were incubated with HDL from CKD rabbit and hemodialysis groups than with HDL from the control group. In both rabbits and humans, platelet aggregation and activation were significantly higher in the presence of HNE-modified HDL than with HDL from their respective controls. Incubation of platelets with a blocking antibody directed against CD36 or with a pharmacologic inhibitor of SRC kinases restored the antiaggregative phenotype in the presence of HDL from CKD rabbits, patients on hemodialysis and peritoneal dialysis, and HNE-modified HDL. Conclusions: HDL from CKD rabbits and patients on hemodialysis exhibited an impaired ability to inhibit platelet aggregation, suggesting that altered HDL properties may contribute to the increased cardiovascular risk in this population. (Copyright © 2020 by the American Society of Nephrology.)
Databáze:	MEDLINE
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