{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:01:57Z","timestamp":1787742117043,"version":"build-2784847793"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Special Talent Scientific Research of Shanxi Provincial Health Commission","award":["2020036"],"award-info":[{"award-number":["2020036"]}]},{"name":"Scientific Research Incentive Fund of Shanxi Cardiovascular Hospital","award":["XYS20200108"],"award-info":[{"award-number":["XYS20200108"]}]},{"name":"Scientific Research Incentive Fund of Shanxi Cardiovascular Hospital","award":["XYS20220101"],"award-info":[{"award-number":["XYS20220101"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myocardial ischemia-reperfusion injury (MIRI) is an important complication in the treatment of heart failure, and its treatment has not made satisfactory progress. Nitroxyl (HNO) showed protective effects on the heart failure, however, the effect and underlying mechanism of HNO on MIRI remain largely unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MIRI model in this study was established to induce H9C2 cell injury through hypoxia\/reoxygenation (H\/R) in vitro. The cell viability was assessed by cell counting kit-8 assay. The effect of HNO on the apoptosis was detected by flow cytometry. DCFH-DA fluorescent probe method was applied to detect the level of intracellular reactive oxygen species (ROS). The morphology of mitochondria and autophagosomes were observed by transmission electron microscopy. Apoptosis, autophagy and PI3K\/Akt\/mTOR pathway-related proteins were detected by western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The viability of H9C2 cells was significantly increased in the HNO group. HNO inhibited apoptosis and regulated expressions of key apoptotic protein, including Bax and Bcl-2. HNO reduced ROS levels and alleviated H\/R-induced mitochondrial damage. HNO also inhibited autophagy and regulated expressions of key autophagy-related molecules, including LC3II, p62 and Beclin1. Further experiments demonstrated that the effects of HNO were mediated through upregulation of PI3K\/Akt\/mTOR pathway. Rapamycin reversed the inhibition of HNO on H\/R-induced autophagy in H9C2 cells, which abrogated the protective effect of HNO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provided the first evidence that HNO protected H\/R-induced cardiomyocytes through inhibiting autophagy via the activation PI3K\/Akt\/mTOR pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0314500","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T13:26:02Z","timestamp":1738157162000},"page":"e0314500","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nitroxyl protects H9C2 cells from H\/R-induced damage and inhibits autophagy via PI3K\/Akt\/mTOR pathway"],"prefix":"10.1371","volume":"20","author":[{"given":"Li","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxuan","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-1451","authenticated-orcid":true,"given":"Yanqing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"issue":"1","key":"pone.0314500.ref001","doi-asserted-by":"crossref","first-page":"30","DOI":"10.31083\/j.rcm2301030","article-title":"Heart failure with mildly reduced ejection fraction: emerging frontiers in clinical characteristics, prognosis, and treatment.","volume":"23","author":"Z Shang","year":"2022","journal-title":"Rev Cardiovasc Med."},{"issue":"10159","key":"pone.0314500.ref002","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"GBD 2017 Disease and Injury Incidence and Prevalence Collaborators","year":"2018","journal-title":"Lancet"},{"issue":"6","key":"pone.0314500.ref003","doi-asserted-by":"crossref","first-page":"e137","DOI":"10.1161\/CIR.0000000000000509","article-title":"2017 ACC\/AHA\/HFSA Focused Update of the 2013 ACCF\/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.","volume":"136","author":"CW Yancy","year":"2017","journal-title":"Circulation"},{"issue":"27","key":"pone.0314500.ref004","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.","volume":"37","author":"P Ponikowski","year":"2016","journal-title":"Eur Heart J"},{"issue":"12","key":"pone.0314500.ref005","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41569-020-0403-y","article-title":"Myocardial ischaemia-reperfusion injury and cardioprotection in perspective","volume":"17","author":"G. 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