Mechanistic Analysis of Nonoxygenated Hypothermic Machine Perfusion’s Protection on Warm Ischemic Kidney Uncovers Greater eNOS Phosphorylation and Vasodilation

Autor: S. Hosni, Clarisse Vandebrouck, N. Chatauret, P. O. Delpech, Rémi Coudroy, M. Scepi, Thierry Hauet
Přispěvatelé: 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), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Scientifique et Technique du Bâtiment (CSTB), Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Université de Tunis El Manar (UTM), Génétique, Expérimentation et Système Innovants (GenESI), Institut National de la Recherche Agronomique (INRA)
Rok vydání: 2014
Předmět:
Male
Pathology
Swine
[SDV]Life Sciences [q-bio]
Vasodilation
Basic (laboratory) research
030204 cardiovascular system & hematology
030230 surgery
Pharmacology
Kidney
TRANSPLANTATION MEDICINE
chemistry.chemical_compound
0302 clinical medicine
Hypothermia
Induced
Ischemia
Enos
Immunology and Allergy
Pharmacology (medical)
Phosphorylation
science
SHEAR-STRESS
biology
organ perfusion and preservation
ACTIVATED PROTEIN-KINASE
ischemia reperfusion injury (IRI)
medicine.anatomical_structure
cellular biology
DCD KIDNEYS
medicine.medical_specialty
Nitric Oxide Synthase Type III
Endothelium
nephrology
kidney transplantation
Cold storage
Nitric oxide
03 medical and health sciences
COLD-STORAGE
medicine
Animals
PRESERVATION
NITRIC-OXIDE SYNTHASE
Transplantation
Machine perfusion
Renal circulation
BLOOD-FLOW
business.industry
donors and donation: donation after circulatory death (DCD)
biology.organism_classification
chemistry
Reperfusion
ENDOTHELIAL DYSFUNCTION
business
RELAXING FACTOR
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: American Journal of Transplantation
American Journal of Transplantation, Wiley, 2014, 14 (11), pp.2500-2514. ⟨10.1111/ajt.12904⟩
ISSN: 1600-6135
1600-6143
DOI: 10.1111/ajt.12904
Popis: International audience; Protection of endothelial cell function may explain the benefits of nonoxygenated hypothermic machine perfusion (MP) for marginal kidney preservation. However, this hypothesis remains to be tested with a preclinical model. We postulated that MP protects the nitric oxide (NO) signaling pathway, altered by static cold storage (CS), and improves renal circulation recovery compared to CS. The endothelium releases the vasodilator NO in response to flow via either increased endothelial NO synthase (eNOS) expression (KLF2-dependent) or activation of eNOS by phosphorylation (via Akt, PKA or AMPK). Using a porcine model of kidney transplantation, including 1 h of warm ischemia and preserved 24 h by CS or MP (n = 5), we reported that MP did not alter the cortical levels of KLF2 and eNOS at the end of preservation, but significantly increased eNOS activating phosphorylation compared to CS. eNOS phosphorylation appeared AMPK-dependent and was concomitant to an increased NO-dependent vasodilation of renal arteries measured, ex situ, at the end of preservation. In vivo, laser Doppler showed that cortical microcirculation was improved at reperfusion in MP kidneys. In conclusion, we demonstrate for the first time, in a large-animal model, that MP protects the NO signaling pathway, confirming the value of MP for marginal kidney preservation.
Databáze: OpenAIRE
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