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Thrombosis in the Coronary Microvasculature Impairs Cardiac Relaxation and Induces Diastolic Dysfunction.

dc.rights.licenseopenen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorROUAULT, Paul
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGUIMBAL, Sarah
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCORNUAULT, Lauriane
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorBOURGUIGNON, Célia
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorFOUSSARD, Ninon
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorALZIEU, Philippe
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorCHOVEAU, Frank
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorBENOIST, David
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCHAPOULY, Candice
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGADEAU, Alain-Pierre
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCOUFFINHAL, Thierry
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorRENAULT, Marie-Ange
dc.date.accessioned2024-03-12T15:31:37Z
dc.date.available2024-03-12T15:31:37Z
dc.date.issued2024-01-01
dc.identifier.issn1524-4636en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/188726
dc.description.abstractEnHeart failure with preserved ejection fraction is proposed to be caused by endothelial dysfunction in cardiac microvessels. Our goal was to identify molecular and cellular mechanisms underlying the development of cardiac microvessel disease and diastolic dysfunction in the setting of type 2 diabetes. We used (leptin receptor-deficient) female mice as a model of type 2 diabetes and heart failure with preserved ejection fraction and identified Hhipl1 (hedgehog interacting protein-like 1), which encodes for a decoy receptor for HH (hedgehog) ligands as a gene upregulated in the cardiac vascular fraction of diseased mice. We then used (desert HH)-deficient mice to investigate the functional consequences of impaired HH signaling in the adult heart. We found that -deficient mice displayed increased end-diastolic pressure while left ventricular ejection fraction was comparable to that of control mice. This phenotype was associated with a reduced exercise tolerance in the treadmill test, suggesting that -deficient mice do present heart failure. At molecular and cellular levels, impaired cardiac relaxation in mice was associated with a significantly decreased PLN (phospholamban) phosphorylation on Thr17 (threonine 17) and an alteration of sarcomeric shortening ex vivo. Besides, as expected, -deficient mice exhibited phenotypic changes in their cardiac microvessels including a prominent prothrombotic phenotype. Importantly, aspirin therapy prevented the occurrence of both diastolic dysfunction and exercise intolerance in these mice. To confirm the critical role of thrombosis in the pathophysiology of diastolic dysfunction, we verified also displays increased cardiac microvessel thrombosis. Moreover, consistently, with -deficient mice, we found that aspirin treatment decreased end-diastolic pressure and improved exercise tolerance in mice. Altogether, these results demonstrate that microvessel thrombosis may participate in the pathophysiology of heart failure with preserved ejection fraction.
dc.language.isoENen_US
dc.subjectarticle recherche
dc.subject.enAnimals
dc.subject.enFemale
dc.subject.enMice
dc.subject.enVentricular Function
dc.subject.enLeft
dc.subject.enStroke Volume
dc.subject.enDiabetes Mellitus
dc.subject.enType 2
dc.subject.enVentricular Dysfunction
dc.subject.enLeft
dc.subject.enHedgehog Proteins
dc.subject.enCardiomyopathies
dc.subject.enHeart Failure
dc.subject.enMicrovessels
dc.subject.enThrombosis
dc.subject.enAspirin
dc.title.enThrombosis in the Coronary Microvasculature Impairs Cardiac Relaxation and Induces Diastolic Dysfunction.
dc.title.alternativeArterioscler Thromb Vasc Biolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1161/ATVBAHA.123.320040en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.identifier.pubmed38031839en_US
bordeaux.journalArteriosclerosis, Thrombosis, and Vascular Biologyen_US
bordeaux.pagee1-e18en_US
bordeaux.volume44en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires (BMC) - UMR 1034en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04501539
hal.version1
hal.date.transferred2024-03-12T15:31:40Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Arteriosclerosis,%20Thrombosis,%20and%20Vascular%20Biology&rft.date=2024-01-01&rft.volume=44&rft.issue=1&rft.spage=e1-e18&rft.epage=e1-e18&rft.eissn=1524-4636&rft.issn=1524-4636&rft.au=ROUAULT,%20Paul&GUIMBAL,%20Sarah&CORNUAULT,%20Lauriane&BOURGUIGNON,%20C%C3%A9lia&FOUSSARD,%20Ninon&rft.genre=article


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