Show simple item record

dc.contributor.authorAhmad, Shiraz
dc.contributor.authorValli, Haseeb
dc.contributor.authorChadda, Karan R
dc.contributor.authorCranley, James
dc.contributor.authorJeevaratnam, Kamalan
dc.contributor.authorHuang, Christopher L-H
dc.date.accessioned2018-09-05T12:44:01Z
dc.date.available2018-09-05T12:44:01Z
dc.date.issued2018-07
dc.identifier.issn0047-6374
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279445
dc.description.abstractINTRODUCTION: Ageing and age-related bioenergetic conditions including obesity, diabetes mellitus and heart failure constitute clinical ventricular arrhythmic risk factors. MATERIALS AND METHODS: Pro-arrhythmic properties in electrocardiographic and intracellular recordings were compared in young and aged, peroxisome proliferator-activated receptor-γ coactivator-1β knockout (Pgc-1β-/-) and wild type (WT), Langendorff-perfused murine hearts, during regular and programmed stimulation (PES), comparing results by two-way ANOVA. RESULTS AND DISCUSSION: Young and aged Pgc-1β-/- showed higher frequencies and durations of arrhythmic episodes through wider PES coupling-interval ranges than WT. Both young and old, regularly-paced, Pgc-1β-/- hearts showed slowed maximum action potential (AP) upstrokes, (dV/dt)max (∼157 vs. 120-130 V s-1), prolonged AP latencies (by ∼20%) and shortened refractory periods (∼58 vs. 51 ms) but similar AP durations (∼50 ms at 90% recovery) compared to WT. However, Pgc-1β-/- genotype and age each influenced extrasystolic AP latencies during PES. Young and aged WT ventricles displayed distinct, but Pgc-1β-/- ventricles displayed similar dependences of AP latency upon (dV/dt)max resembling aged WT. They also independently increased myocardial fibrosis. AP wavelengths combining activation and recovery terms paralleled contrasting arrhythmic incidences in Pgc-1β-/- and WT hearts. Mitochondrial dysfunction thus causes pro-arrhythmic Pgc-1β-/- phenotypes by altering AP conduction through reducing (dV/dt)max and causing age-dependent fibrotic change.
dc.description.sponsorshipWellcome Trust, MRC, BHF, Sudden Adult Death Syndrome (SADS) UK society, and the Fundamental Research Grant Scheme (Ministry of Education, Malaysia)
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectMyocardium
dc.subjectMitochondria, Heart
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectMice
dc.subjectFibrosis
dc.subjectAction Potentials
dc.subjectAging
dc.subjectModels, Cardiovascular
dc.subjectArrhythmias, Cardiac
dc.subjectPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
dc.titleVentricular pro-arrhythmic phenotype, arrhythmic substrate, ageing and mitochondrial dysfunction in peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β-/-) murine hearts.
dc.typeArticle
prism.endingPage103
prism.publicationDate2018
prism.publicationNameMech Ageing Dev
prism.startingPage92
prism.volume173
dc.identifier.doi10.17863/CAM.26819
dcterms.dateAccepted2018-05-11
rioxxterms.versionofrecord10.1016/j.mad.2018.05.004
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2018-07
dc.contributor.orcidHuang, Christopher [0000-0001-9553-6112]
dc.identifier.eissn1872-6216
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/M001288/1)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idWellcome Trust (105727/Z/14/Z)
pubs.funder-project-idBritish Heart Foundation (PG/15/12/31280)
cam.issuedOnline2018-05-12


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

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