YAP mediates compensatory cardiac hypertrophy through aerobic glycolysis in response to pressure overload

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dc.contributor.authorKashihara, Toshihideen
dc.contributor.authorMukai, Risaen
dc.contributor.authorOka, Shin-ichi I.en
dc.contributor.authorZhai, Peiyongen
dc.contributor.authorNakada, Yasukien
dc.contributor.authorYang, Zhien
dc.contributor.authorMizushima, Wataruen
dc.contributor.authorNakahara, Tsutomuen
dc.contributor.authorWarren, Junco S.en
dc.contributor.authorAbdellatif, Mahaen
dc.contributor.authorSadoshima, Junichien
dc.date.accessioned2023-01-17T14:01:21Zen
dc.date.available2023-01-17T14:01:21Zen
dc.date.issued2022-03-15en
dc.date.updated2023-01-14T14:29:02Zen
dc.description.abstractThe heart utilizes multiple adaptive mechanisms to maintain pump function. Compensatory cardiac hypertrophy reduces wall stress and oxygen consumption, thereby protecting the heart against acute blood pressure elevation. The nuclear effector of the Hippo pathway, Yes-associated protein 1 (YAP), is activated and mediates compensatory cardiac hypertrophy in response to acute pressure overload (PO). In this study, YAP promoted glycolysis by upregulating glucose transporter 1 (GLUT1), which in turn caused accumulation of intermediates and metabolites of the glycolytic, auxiliary, and anaplerotic pathways during acute PO. Cardiac hypertrophy was inhibited and heart failure was exacerbated in mice with YAP haploinsufficiency in the presence of acute PO. However, normalization of GLUT1 rescued the detrimental phenotype. PO induced the accumulation of glycolytic metabolites, including l-serine, l-aspartate, and malate, in a YAP-dependent manner, thereby promoting cardiac hypertrophy. YAP upregulated the GLUT1 gene through interaction with TEA domain family member 1 (TEAD1) and HIF-1α in cardiomyocytes. Thus, YAP induces compensatory cardiac hypertrophy through activation of the Warburg effect.en
dc.description.versionPublished versionen
dc.format.extent22 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e150595 (Article number)en
dc.identifier.doihttps://doi.org/10.1172/JCI150595en
dc.identifier.eissn1558-8238en
dc.identifier.issn0021-9738en
dc.identifier.issue6en
dc.identifier.orcidWarren, Junko [0000-0001-5231-4181]en
dc.identifier.other150595 (PII)en
dc.identifier.pmid35133975en
dc.identifier.urihttp://hdl.handle.net/10919/113191en
dc.identifier.volume132en
dc.language.isoenen
dc.publisherAmerican Society for Clinical Investigationen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000772266400004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectHEART-FAILUREen
dc.subjectMETABOLISMen
dc.subjectAPOPTOSISen
dc.subjectGROWTHen
dc.subjectACTIVATIONen
dc.subjectAUTOPHAGYen
dc.subjectPREVENTSen
dc.subjectMYOCYTESen
dc.subjectGLUT1en
dc.subjectCardiologyen
dc.subjectCardiovascular diseaseen
dc.subjectHeart Diseaseen
dc.subjectGeneticsen
dc.subjectHeart Disease - Coronary Heart Diseaseen
dc.subjectCardiovascularen
dc.subject2 Aetiologyen
dc.subject2.1 Biological and endogenous factorsen
dc.subject.meshMyocytes, Cardiacen
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshCardiomegalyen
dc.subject.meshCitric Acid Cycleen
dc.subject.meshGlycolysisen
dc.subject.meshGlucose Transporter Type 1en
dc.subject.meshYAP-Signaling Proteinsen
dc.titleYAP mediates compensatory cardiac hypertrophy through aerobic glycolysis in response to pressure overloaden
dc.title.serialJournal of Clinical Investigationen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2022-02-03en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Biomedical Research Institute at VTCen

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