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dc.contributor.authorHoe, Louise E See
dc.contributor.authorSchilling, Jan M
dc.contributor.authorTarbit, Emiri
dc.contributor.authorKiessling, Can J
dc.contributor.authorBusija, Anna R
dc.contributor.authorNiesman, Ingrid R
dc.contributor.authorDu Toit, Eugene
dc.contributor.authorAshton, Kevin J
dc.contributor.authorRoth, David M
dc.contributor.authorHeadrick, John P
dc.contributor.authorPatel, Hemal H
dc.contributor.authorPeart, Jason N
dc.date.accessioned2017-05-03T12:46:10Z
dc.date.available2017-05-03T12:46:10Z
dc.date.issued2014
dc.identifier.issn0363-6135
dc.identifier.doi10.1152/ajpheart.00081.2014
dc.identifier.urihttp://hdl.handle.net/10072/65640
dc.description.abstractCholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemia-reperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-β-cyclodextrin (MβCD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function, I/R tolerance, and opioid receptor (OR)-mediated protection. Langendorff-perfused hearts from young male C57Bl/6 mice were untreated or treated with 0.02–1.0 mM MβCD for 25 min to deplete membrane cholesterol and disrupt caveolae. Hearts were subjected to 25-min ischemia/45-min reperfusion, and the cardioprotective effects of morphine applied either acutely or chronically [sustained ligand-activated preconditioning (SLP)] were assessed. MβCD concentration dependently reduced normoxic contractile function and postischemic outcomes in association with graded (10–30%) reductions in sarcolemmal cholesterol. Cardioprotection with acute morphine was abolished with ≥20 μM MβCD, whereas SLP was more robust and only inhibited with ≥200 μM MβCD. Deletion of Cav-3 also reduced, whereas Cav-3 OE improved, myocardial I/R tolerance. Protection via SLP remained equally effective in Cav-3 KO mice and was additive with innate protection arising with Cav-3 OE. These data reveal the membrane cholesterol dependence of normoxic myocardial and coronary function, I/R tolerance, and OR-mediated cardioprotection in murine hearts (all declining with cholesterol depletion). In contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R tolerance parallels Cav-3 expression. Novel SLP appears unique, being less sensitive to cholesterol depletion than acute OR protection and arising independently of Cav-3 expression.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Physiological Society
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefromH895
dc.relation.ispartofpagetoH903
dc.relation.ispartofissue6
dc.relation.ispartofjournalAmerican Journal of Physiology Heart and Circulatory Physiology
dc.relation.ispartofvolume307
dc.rights.retentionY
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchMedical physiology not elsewhere classified
dc.subject.fieldofresearchCardiovascular medicine and haematology
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode3208
dc.subject.fieldofresearchcode320899
dc.subject.fieldofresearchcode3201
dc.titleSarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Medical Science
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
gro.hasfulltextNo Full Text
gro.griffith.authorHeadrick, John P.
gro.griffith.authorPeart, Jason N.
gro.griffith.authorDu Toit, Eugene


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