{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:07:58Z","timestamp":1792552078799,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T00:00:00Z","timestamp":1493251200000},"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":["81030002"],"award-info":[{"award-number":["81030002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81270186"],"award-info":[{"award-number":["81270186"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81441008"],"award-info":[{"award-number":["81441008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81102079"],"award-info":[{"award-number":["81102079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2017,8]]},"abstract":"Abstract<\/jats:title>\n \n The cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes. However, microvascular ischemia\/reperfusion injury (\n IRI<\/jats:styled-content>\n ) following percutaneous coronary intervention is a woefully neglected topic, and few strategies are available to reverse such pathologies. Here, we studied the effects of melatonin on microcirculation\n IRI<\/jats:styled-content>\n and elucidated the underlying mechanism. Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow, and lower microcirculation perfusion defects. Histological analysis showed that cardiac microcirculation endothelial cells (\n CMEC<\/jats:styled-content>\n ) in melatonin\u2010treated mice had an unbroken endothelial barrier, increased endothelial nitric oxide synthase expression, unobstructed lumen, reduced inflammatory cell infiltration, and less endothelial damage. In contrast, AMP\u2010activated protein kinase \u03b1 (\n AMPK<\/jats:styled-content>\n \u03b1) deficiency abolished the beneficial effects of melatonin on microvasculature. In vitro,\n IRI<\/jats:styled-content>\n activated dynamin\u2010related protein 1 (Drp1)\u2010dependent mitochondrial fission, which subsequently induced voltage\u2010dependent anion channel 1 (\n VDAC<\/jats:styled-content>\n 1) oligomerization, hexokinase 2 (\n HK<\/jats:styled-content>\n 2) liberation, mitochondrial permeability transition pore (\n mPTP<\/jats:styled-content>\n ) opening,\n PINK<\/jats:styled-content>\n 1\/Parkin upregulation, and ultimately mitophagy\u2010mediated\n CMEC<\/jats:styled-content>\n death. However, melatonin strengthened\n CMEC<\/jats:styled-content>\n survival via activation of\n AMPK<\/jats:styled-content>\n \u03b1, followed by p\u2010Drp1\n S616<\/jats:sup>\n downregulation and p\u2010Drp1\n S37<\/jats:sup>\n upregulation, which blunted Drp1\u2010dependent mitochondrial fission. Suppression of mitochondrial fission by melatonin recovered\n VDAC<\/jats:styled-content>\n 1\u2010\n HK<\/jats:styled-content>\n 2 interaction that prevented\n mPTP<\/jats:styled-content>\n opening and\n PINK<\/jats:styled-content>\n 1\/Parkin activation, eventually blocking mitophagy\u2010mediated cellular death. In summary, this study confirmed that melatonin protects cardiac microvasculature against\n IRI<\/jats:styled-content>\n . The underlying mechanism may be attributed to the inhibitory effects of melatonin on mitochondrial fission\u2010\n VDAC<\/jats:styled-content>\n 1\u2010\n HK<\/jats:styled-content>\n 2\u2010\n mPTP<\/jats:styled-content>\n \u2010mitophagy axis via activation of AMPK\u03b1.\n <\/jats:p>","DOI":"10.1111\/jpi.12413","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T10:17:23Z","timestamp":1491905843000},"source":"Crossref","is-referenced-by-count":346,"title":["Melatonin protects cardiac microvasculature against ischemia\/reperfusion injury via suppression of mitochondrial fission\u2010\n VDAC<\/scp>\n 1\u2010\n HK<\/scp>\n 2\u2010\n mPTP<\/scp>\n \u2010mitophagy axis"],"prefix":"10.1111","volume":"63","author":[{"given":"Hao","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiology Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunying","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Department of Radiation Oncology Peking University Cancer Hospital and Institute Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhua","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2252-8992","authenticated-orcid":false,"given":"Yundai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chinese PLA General Hospital Beijing 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