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Scaffolding hypothesis of aging: role of caveolin‐3 in the aged myocardium
Author(s) -
Fridolfsson Heidi Nicole,
Reichelt Melissa,
Peart Jason,
Niesman Ingrid,
Head Brian,
Kidd Michael,
Patel Piyush,
Headrick John,
Roth David,
Patel Hemal
Publication year - 2011
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.25.1_supplement.828.10
The aged heart is more susceptible to injury and less responsive to interventions that are protective against ischemia‐reperfusion in young hearts. We hypothesized that defects of the aged myocardium are a consequence of lost scaffolds to organize cellular signaling; therefore, we examined the contribution of caveolin‐3 (Cav‐3), an integral scaffolding protein in the heart, to ischemic tolerance in aged myocardium. Protein expression analysis revealed 50% reduction in Cav‐3 protein at 2 years of age and a near complete loss of morphologic caveolae. Cardiac myocyte‐specific overexpression of Cav‐3 (Cav‐3 OE) increased Cav‐3 expression and caveolae formation through 2 years of age. Cav‐3 OE mice showed augmented ischemic tolerance in both young and aged hearts as assessed in the Langendorff perfused heart. Additionally, the ratio of mitochondrial area to number was dramatically reduced in aged mice. This ratio was maintained with age in the Cav‐3 OE mice along with increased expression of OPA1, suggesting Cav‐3 as a potential regulator of mitochondrial dynamics. These data reveal a parallel decline in cardiac ischemic tolerance and Cav‐3 expression, and indicate that overexpression of Cav‐3 can eliminate this decline. Therapies to drive Cav‐3 expression may be a novel means to limit cardiac aging.