{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:06:28Z","timestamp":1792098388541,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T00:00:00Z","timestamp":1520380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81300063"],"award-info":[{"award-number":["81300063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2014A030313501A"],"award-info":[{"award-number":["2014A030313501A"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Obstructive sleep apnoea (<jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>) characterized by intermittent hypoxia (<jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>) is closely associated with cardiovascular diseases. <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content> confers cardiac injury via accelerating cardiomyocyte apoptosis, whereas the underlying mechanism has remained largely enigmatic. This study aimed to explore the potential mechanisms involved in the <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\u2010induced cardiac damage performed with the <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\u2010exposed cell and animal models and to investigate the protective effects of haemin, a potent haeme oxygenase\u20101 (<jats:styled-content style=\"fixed-case\">HO<\/jats:styled-content>\u20101) activator, on the cardiac injury induced by <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>. Neonatal rat cardiomyocyte (<jats:styled-content style=\"fixed-case\">NRC<\/jats:styled-content>) was treated with or without haemin before <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content> exposure. Eighteen male Sprague\u2010Dawley (<jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>) rats were randomized into three groups: control group, <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content> group (<jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>, ip) and <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\u00a0+\u00a0haemin group (haemin, 4\u00a0mg\/kg, ip). The cardiac function was determined by echocardiography. Mitochondrial fission was evaluated by Mitotracker staining. The mitochondrial dynamics\u2010related proteins (mitochondrial fusion protein, Mfn2; mitochondrial fission protein, Drp1) were determined by Western blot. The apoptosis of cardiomyocytes and heart sections was examined by <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content> regulated mitochondrial dynamics\u2010related proteins (decreased Mfn2 and increased Drp1 expressions, respectively), thereby leading to mitochondrial fragmentation and cell apoptosis in cardiomyocytes in\u00a0vitro and in\u00a0vivo, while haemin\u2010induced <jats:styled-content style=\"fixed-case\">HO<\/jats:styled-content>\u20101 up\u2010regulation attenuated <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\u2010induced mitochondrial fragmentation and cell apoptosis. Moreover, <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content> resulted in left ventricular hypertrophy and impaired contractile function in\u00a0vivo, while haemin ameliorated <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\u2010induced cardiac dysfunction. This study demonstrates that pharmacological activation of <jats:styled-content style=\"fixed-case\">HO<\/jats:styled-content>\u20101 pathway protects against <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\u2010induced cardiac dysfunction and myocardial fibrosis through the inhibition of mitochondrial fission and cell apoptosis.<\/jats:p>","DOI":"10.1111\/jcmm.13560","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T12:58:33Z","timestamp":1520427513000},"page":"2717-2726","source":"Crossref","is-referenced-by-count":36,"title":["Haemin attenuates intermittent hypoxia\u2010induced cardiac injury via inhibiting mitochondrial fission"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4806-222X","authenticated-orcid":false,"given":"Qian","family":"Han","sequence":"first","affiliation":[{"name":"State Key Laboratory Guangzhou Institute of Respiratory Health Department of Respiratory Medicine The First Affiliated Hospital of Guangzhou Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory Guangzhou Institute of Respiratory Health Department of Respiratory Medicine The First Affiliated Hospital of Guangzhou Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary SiuMan","family":"Ip","sequence":"additional","affiliation":[{"name":"Li Kashing Faculty of Medicine Department of Medicine The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Li Kashing Faculty of Medicine Department of Medicine The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhen","sequence":"additional","affiliation":[{"name":"Li Kashing Faculty of Medicine Department of Medicine The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith ChoiWo","family":"Mak","sequence":"additional","affiliation":[{"name":"Li Kashing Faculty of Medicine Department of Medicine The University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuofu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory Guangzhou Institute of Respiratory Health Department of Respiratory Medicine The First Affiliated Hospital of Guangzhou Medical University Guangzhou 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