Diet-induced increase in plasma oxidized LDL promotes early fibrosis in a renal porcine auto-transplantation model

Autor: Frédéric Favreau, Ludivine Rossard, Antoine Thierry, Thierry Hauet, Sylvain Le Pape, N. Chatauret, Sébastien Giraud, Lilach O. Lerman
Přispěvatelé: Service de Biochimie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Expérimentation et Système Innovants (GenESI), Institut National de la Recherche Agronomique (INRA), Division of Nephrology and Hypertension, Mayo Clinic, This study was supported by research grants from Société de Néphrologie (Subvention Amgen), Fondation transplantation, Conseil Général de la Vienne and Conseil Régional Poitou-Charentes. NC is a recipient of a FEDER grant (#34474)., BMC, Ed., Ischémie - Reperfusion en transplatation rénale, European Society for Organ Transplantation (ESOT). INT., ProdInra, Migration, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Hauet, Thierry
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
[SDV]Life Sciences [q-bio]
Sus scrofa
030204 cardiovascular system & hematology
Kidney
Kidney Function Tests
[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
Kidney transplantation
ischémie reperfusion
0302 clinical medicine
Fibrosis
Transforming Growth Factor beta
ComputingMilieux_MISCELLANEOUS
Medicine(all)
0303 health sciences
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
biology
General Medicine
Arteries
Extracellular matrix
3. Good health
[SDV] Life Sciences [q-bio]
Lipoproteins
LDL
Proteinuria
Receptors
Oxidized LDL
medicine.anatomical_structure
Cholesterol
Creatinine
Models
Animal
lipids (amino acids
peptides
and proteins)
Signal Transduction
Oxidized LDL
medicine.medical_specialty
Endothelium
Hypercholesterolemia
matrice extracellulaire
hypercholestérolemie
Diet
High-Fat
Transplantation
Autologous
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Internal medicine
Ischemia reperfusion
Preclinical model
TGF beta signaling pathway
medicine
Animals
Humans
Vimentin
lipoprotéine de faible densite
Scavenger receptor
Antibodies
Blocking
030304 developmental biology
transplantation rénale
Biochemistry
Genetics and Molecular Biology(all)
business.industry
Research
Endothelial Cells
Transforming growth factor beta
medicine.disease
[SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
Transplantation
Endocrinology
biology.protein
business
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Journal of Translational Medicine
Journal of Translational Medicine, BioMed Central, 2014, 12 (1), pp.76. ⟨10.1186/1479-5876-12-76⟩
Transplant International
15. Congress of the ESOT
15. Congress of the ESOT, European Society for Organ Transplantation (ESOT). INT., Sep 2011, Glasgow, United Kingdom
Journal of Translational Medicine (12), . (2014)
ISSN: 1479-5876
DOI: 10.1186/1479-5876-12-76⟩
Popis: International audience; BACKGROUND: In kidney transplantation, the prevalence of hypercholesterolemia as a co-morbidity factor known to affect graft function, is rising due to the increased number of older donors in response to organ shortage as well as to the hyperlipidemic effects of immunosuppressors in recipient. This study aimed to characterize the effects of hypercholesterolemia on renal graft outcome, investigating the role of oxidized low-density lipoprotein (OxLDL). METHODS: In vivo, we used a porcine preclinical model of renal auto-transplantation modulated by two experimental diets: a normal (n = 6) or a hyperlipidemic diet (n = 5) maintained during the 3 month follow-up after the surgical procedure. Kidney function and OxLDL levels were monitored as well as fibrosis, LOX-1 and TGF beta signaling pathways. In vitro, we used human artery endothelial cells subjected to OxLDL to investigate the TGF beta profibrotic pathway and the role of the scavenger receptor LOX-1. RESULTS: Hyperlipidemic diet-induced increase in plasma OxLDL levels at the time of surgery correlated with an increase in proteinuria 3 months after transplantation, associated with an early graft fibrosis combined with an activation of renal TGF beta signaling. These data suggest a direct involvement of OxLDL in the hyperlipidemic diet-induced activation of the pro-fibrotic TGF beta pathway which seems to be activated by LOX-1 signaling. These results were supported by studies with endothelial cells incubated in culture medium containing OxLDL promoting TGF beta expression inhibited by LOX-1 antibody. CONCLUSIONS: These results implicate OxLDL in the hyperlipidemic diet-promoted fibrosis in transplanted kidneys, suggesting LOX-1 as a potential therapeutic target and reinforce the need to control cholesterol levels in kidney transplant recipients.
Databáze: OpenAIRE
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