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http://purl.uniprot.org/citations/18936328http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18936328http://www.w3.org/2000/01/rdf-schema#comment"

Background

Caveolae, lipid-rich microdomains of the sarcolemma, localize and enrich cardiac-protective signaling molecules. Caveolin-3 (Cav-3), the dominant isoform in cardiac myocytes, is a determinant of caveolar formation. We hypothesized that cardiac myocyte-specific overexpression of Cav-3 would enhance the formation of caveolae and augment cardiac protection in vivo.

Methods and results

Ischemic preconditioning in vivo increased the formation of caveolae. Adenovirus for Cav-3 increased caveolar formation and phosphorylation of survival kinases in cardiac myocytes. A transgenic mouse with cardiac myocyte-specific overexpression of Cav-3 (Cav-3 OE) showed enhanced formation of caveolae on the sarcolemma. Cav-3 OE mice subjected to ischemia/reperfusion injury had a significantly reduced infarct size relative to transgene-negative mice. Endogenous cardiac protection in Cav-3 OE mice was similar to wild-type mice undergoing ischemic preconditioning; no increased protection was observed in preconditioned Cav-3 OE mice. Cav-3 knockout mice did not show endogenous protection and showed no protection in response to ischemic preconditioning. Cav-3 OE mouse hearts had increased basal Akt and glycogen synthase kinase-3beta phosphorylation comparable to wild-type mice exposed to ischemic preconditioning. Wortmannin, a phosphoinositide 3-kinase inhibitor, attenuated basal phosphorylation of Akt and glycogen synthase kinase-3beta and blocked cardiac protection in Cav-3 OE mice. Cav-3 OE mice had improved functional recovery and reduced apoptosis at 24 hours of reperfusion.

Conclusions

Expression of caveolin-3 is both necessary and sufficient for cardiac protection, a conclusion that unites long-standing ultrastructural and molecular observations in the ischemic heart. The present results indicate that increased expression of caveolins, apparently via actions that depend on phosphoinositide 3-kinase, has the potential to protect hearts exposed to ischemia/reperfusion injury."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.108.788331"xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Ishikawa Y."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Miyanohara A."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Niesman I.R."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Hagiwara Y."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Insel P.A."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Roth D.M."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Head B.P."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Patel P.M."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Yokoyama U."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Patel H.H."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Tsutsumi Y.M."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Horikawa Y.T."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Jennings M.M."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/author"Kidd M.W."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/pages"1979-1988"xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/title"Cardiac-specific overexpression of caveolin-3 induces endogenous cardiac protection by mimicking ischemic preconditioning."xsd:string
http://purl.uniprot.org/citations/18936328http://purl.uniprot.org/core/volume"118"xsd:string
http://purl.uniprot.org/citations/18936328http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18936328
http://purl.uniprot.org/citations/18936328http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18936328
http://purl.uniprot.org/uniprot/P56539#attribution-1B3F3FDD8F0C8F708BB9523C8AB8C129http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/18936328
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