{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:30:11Z","timestamp":1787668211593,"version":"build-2736575974"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T00:00:00Z","timestamp":1543449600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["13SDG14660064"],"award-info":[{"award-number":["13SDG14660064"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HL125436"],"award-info":[{"award-number":["R01 HL125436"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Li Ka Shing Sino-Canadian Exchange Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cardiac remodelling in the ischaemic heart determines prognosis in patients with ischaemic heart disease (IHD), while enhancement of angiogenesis and cell survival has shown great potential for IHD despite translational challenges. Phosphoinositide 3-kinase (PI3K)\/Akt signalling pathways play a critical role in promoting angiogenesis and cell survival. However, the effect of PI3K\u03b2 in the ischaemic heart is poorly understood. This study investigates the role of endothelial and cardiomyocyte (CM) PI3K\u03b2 in post-infarct cardiac remodelling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>PI3K\u03b2 catalytic subunit-p110\u03b2 level was increased in infarcted murine and human hearts. Using cell type-specific loss-of-function approaches, we reported novel and distinct actions of p110\u03b2 in endothelial cells (ECs) vs. CMs in response to myocardial ischaemic injury. Inactivation of endothelial p110\u03b2 resulted in marked resistance to infarction and adverse cardiac remodelling with decreased mortality, improved systolic function, preserved microvasculature, and enhanced Akt activation. Cultured ECs with p110\u03b2 knockout or inhibition displayed preferential PI3K\u03b1\/Akt\/endothelial nitric oxide synthase signalling that consequently promoted protective signalling and angiogenesis. In contrast, mice with CM p110\u03b2-deficiency exhibited adverse post-infarct ventricular remodelling with larger infarct size and deteriorated cardiac function, which was due to enhanced susceptibility of CMs to ischaemia-mediated cell death. Disruption of CM p110\u03b2 signalling compromised nuclear p110\u03b2 and phospho-Akt levels leading to perturbed gene expression and elevated pro-cell death protein levels, increasing the susceptibility to CM death. A similar divergent response of PI3K\u03b2 endothelial and CM mutant mice was seen using a model of myocardial ischaemia\u2013reperfusion injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data demonstrate novel, differential, and cell-specific functions of PI3K\u03b2 in the ischaemic heart. While the loss of endothelial PI3K\u03b2 activity produces cardioprotective effects, CM PI3K\u03b2 is protective against myocardial ischaemic injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvy298","type":"journal-article","created":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T15:12:50Z","timestamp":1543331570000},"page":"1343-1356","source":"Crossref","is-referenced-by-count":22,"title":["Endothelial and cardiomyocyte PI3K\u03b2 divergently regulate cardiac remodelling in response to ischaemic injury"],"prefix":"10.1093","volume":"115","author":[{"given":"Xueyi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Zhabyeyev","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abul K","family":"Azad","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Wang","sequence":"additional","affiliation":[{"name":"Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Department of Physiology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A","family":"Minerath","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, Francois M. 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