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Cardiac myocyte‐specific overexpression of caveolin‐3 enhances β‐adrenergic signaling and response in young and aged mice (850.8)
Author(s) -
Busija Anna,
Roth David,
Insel Paul,
Patel Hemal
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.850.8
Subject(s) - phospholamban , caveolin 3 , caveolae , endocrinology , medicine , chronotropic , inotrope , agonist , myocyte , receptor , cardiac function curve , caveolin , genetically modified mouse , transgene , biology , microbiology and biotechnology , chemistry , signal transduction , heart failure , heart rate , biochemistry , gene , blood pressure
Caveolins (Cavs) are scaffolding proteins essential to the formation of caveolae, membrane domains that compartmentalize numerous signaling molecules, including β‐adrenergic receptors (β‐ARs). A decrease in Cav proteins with aging may contribute to age‐associated loss in cardiac function. By contrast, mice with cardiac myocyte (CM)‐specific overexpression of Cav‐3 (Cav‐3 OE) have more caveolae in CMs and are protected from age‐associated cardiovascular dysfunction. β‐AR agonists increase inotropy and chronotropy but whether increased Cav‐3 expression alters β‐AR response as a means to preserve cardiovascular function with age is unknown. We treated Langendorff‐perfused hearts from young and aged transgene‐negative (TGneg) and Cav‐3 OE mice with the β‐AR agonist isoproterenol (Iso). Cav‐3 OE mice had augmented Iso‐stimulated inotropy (+dP/dt) and lusitropy (‐dP/dt) relative to TGneg, and CMs isolated from Cav‐3 OE mice have increased cAMP production and phospholamban phosphorylation in response to Iso. Moreover, aged (20‐22 month‐old) Cav‐3 OE mice have preserved β‐AR‐stimulated inotropy and lusitropy compared to age‐matched TGneg mice. Thus, increased expression of Cav‐3 enhances β‐AR‐promoted contractile function in both young and aged mice. Increase in Cav‐3 expression may be a way to enhance cardiac β‐AR response throughout the life span. Grant Funding Source : Supported by NIH HL107200