{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:20:58Z","timestamp":1790259658050,"version":"4.1.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"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":["82260057"],"award-info":[{"award-number":["82260057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Plan Project of Zunyi","award":["zunshikehe HZ (2023)227"],"award-info":[{"award-number":["zunshikehe HZ (2023)227"]}]},{"name":"Research Foundation for Master Scholar of Zunyi Medical University","award":["yuanzi (2016)29"],"award-info":[{"award-number":["yuanzi (2016)29"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cardiomyocyte hypoxia-reoxygenation (HR) is considered as a major cause of heart failure. Pinacidil is a classic ATP sensitive potassium channel opener and plays a crucial role in cardiomyocyte HR injuries. However, the specific mechanism is poorly understood. We established HR rat model and introduced 5-Hydroxydecanoate (5-HD), N-(2-Mercaptopropionyl)-glycine (MPG), and Dimethylethylenediylglycine (DMOG) to investigate the protection of Pinacidil (P) on\u00a0cardiomyocyte. HE staining, electron microscopy and JC-1 staining were used to observe mitochondrial structure and mitochondrial membrane potential (MMP). Reactive oxygen species (ROS), hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), vascular endothelial growth factor A (VEGF-A), heme oxygenase-1 (HO-1), and induced nitric oxide synthase (iNOS) were analyzed in this study. Network pharmacology analysis and auto-docking were used to predict the possible target of Pinadicil under cardiomyocyte HR condition. The integrity of mitochondrial structure and MMP were effectively promoted in P and MPG+DMOG\u2009+\u2009P groups. ROS was significantly increased after HR, treatment with P or MPG+DMOG\u2009+\u2009P, the content of ROS was increased. The expressions of HIF-1\u03b1, VEGF-A, HO-1 and iNOS were significantly increased in P and MPG+DMOG\u2009+\u2009P groups compared with HR group. Docking results confirmed that prolyl hydroxylase (PHD) was the most possible target for unsaturated binding with Pinacidil guanidine. Altogether, these data indicate that Pinacidil up-regulated and activated HIF-1\u03b1 protein to protect caridomyocytes against HR injuries and the mechanism may be related to Pinacidil guanidine binding to PHD.<\/jats:p>","DOI":"10.1371\/journal.pone.0318859","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T13:43:53Z","timestamp":1740404633000},"page":"e0318859","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Protective effect of Pinacidil on hypoxic-reoxygenated cardiomyocytes in vitro and in vivo via HIF-1\u03b1\/HRE 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