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LY20H020004"],"award-info":[{"award-number":["Project Nos. LY20H020004"]}]},{"name":"Medical and Health Science Program of Zhejiang Province","award":["(No.2018278178)"],"award-info":[{"award-number":["(No.2018278178)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Both calcium-independent phospholipase A2 beta (iPLA2\u03b2) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2\u03b2 is increased during myocardial ischemia\/reperfusion (I\/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2\u03b2 in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I\/R injury models are significantly elevated. Further, iPLA2\u03b2 knockout mice and siRNA mediated iPLA2\u03b2 knockdown are employed to evaluate the ER stress and cell apoptosis during I\/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2\u03b2. Our data demonstrate the increase of iPLA2\u03b2 augments ER stress and enhances cardiomyocyte apoptosis during I\/R injury in vitro and in vivo. Inhibition of iPLA2\u03b2 ameliorates ER stress and decreases cell death. Mechanistically, iPLA2\u03b2 promotes ER stress and apoptosis by translocating to ER upon myocardial I\/R injury. Together, our study suggests iPLA2\u03b2 contributes to ER stress-induced apoptosis during myocardial I\/R injury, which may serve as a potential therapeutic target against ischemic heart disease.<\/jats:p>","DOI":"10.3390\/cells10061446","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T14:16:04Z","timestamp":1623248164000},"page":"1446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["iPLA2\u03b2 Contributes to ER Stress-Induced Apoptosis during Myocardial Ischemia\/Reperfusion Injury"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5896-7092","authenticated-orcid":false,"given":"Tingting","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China"},{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China"},{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingchao","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China"},{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xukun","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shasha","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingbo","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China"},{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaweng","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-9570","authenticated-orcid":false,"given":"Wenbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meihui","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7027-0717","authenticated-orcid":false,"given":"Guosheng","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China"},{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1172\/JCI62874","article-title":"Myocardial ischemia-reperfusion injury: A neglected therapeutic target","volume":"123","author":"Hausenloy","year":"2013","journal-title":"J. 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