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dc.contributor.authorMethner, Carmen
dc.contributor.authorChouchani, Edward T
dc.contributor.authorBuonincontri, Guido
dc.contributor.authorPell, Victoria R
dc.contributor.authorSawiak, Stephen
dc.contributor.authorMurphy, Mike
dc.contributor.authorKrieg, Thomas
dc.date.accessioned2021-10-07T23:30:22Z
dc.date.available2021-10-07T23:30:22Z
dc.date.issued2014-07
dc.identifier.issn1388-9842
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329112
dc.description.abstractAIMS: Recently it has been shown that the mitochondria-targeted S-nitrosothiol MitoSNO protects against acute ischaemia/reperfusion (IR) injury by inhibiting the reactivation of mitochondrial complex I in the first minutes of reperfusion of ischaemic tissue, thereby preventing free radical formation that underlies IR injury. However, it remains unclear how this transient inhibition of mitochondrial complex I-mediated free radicals at reperfusion affects the long-term recovery of the heart following IR injury. Here we determined whether the acute protection by MitoSNO at reperfusion prevented the subsequent development of post-myocardial infarction heart failure. METHODS AND RESULTS: Mice were subjected to 30 min left coronary artery occlusion followed by reperfusion and recovery over 28 days. MitoSNO (100 ng/kg) was applied 5 min before the onset of reperfusion followed by 20 min infusion (1 ng/kg/min). Infarct size and cardiac function were measured by magnetic resonance imaging (MRI) 24 h after infarction. MitoSNO-treated mice exhibited reduced infarct size and preserved function. In addition, MitoSNO at reperfusion improved outcome measures 28 days post-IR, including preserved systolic function (63.7 ±1.8% LVEF vs. 53.7 ± 2.1% in controls, P = 0.01) and tissue fibrosis. CONCLUSIONS: MitoSNO action acutely at reperfusion reduces infarct size and protects from post-myocardial infarction heart failure. Therefore, targeted inhibition of mitochondrial complex I in the first minutes of reperfusion by MitoSNO is a rational therapeutic strategy for preventing subsequent heart failure in patients undergoing IR injury.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherWiley
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectMyocardium
dc.subjectHeart
dc.subjectMitochondria
dc.subjectMyocytes, Cardiac
dc.subjectAnimals
dc.subjectMice
dc.subjectMyocardial Reperfusion Injury
dc.subjectMyocardial Infarction
dc.subjectFree Radicals
dc.subjectS-Nitrosothiols
dc.subjectElectron Transport Complex I
dc.subjectMitochondrial Proteins
dc.subjectNitric Oxide Donors
dc.subjectMagnetic Resonance Imaging, Cine
dc.subjectNitrosation
dc.subjectHeart Failure
dc.subjectCoronary Occlusion
dc.titleMitochondria selective S-nitrosation by mitochondria-targeted S-nitrosothiol protects against post-infarct heart failure in mouse hearts.
dc.typeArticle
prism.endingPage717
prism.issueIdentifier7
prism.publicationDate2014
prism.publicationNameEur J Heart Fail
prism.startingPage712
prism.volume16
dc.identifier.doi10.17863/CAM.76558
dcterms.dateAccepted2014-03-28
rioxxterms.versionofrecord10.1002/ejhf.100
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2014-07
dc.contributor.orcidSawiak, Stephen [0000-0003-4210-9816]
dc.contributor.orcidMurphy, Mike [0000-0003-1115-9618]
dc.contributor.orcidKrieg, Thomas [0000-0002-5192-580X]
dc.identifier.eissn1879-0844
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (MC_U105663142)
cam.issuedOnline2014-05-31


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International