Caveolin and the aged myocardium

Abstract

The aged heart is more susceptible to ischemic injury than the young heart. We hypothesized that loss of efficiency via reduced cellular scaffolds leads to this susceptibility. We examined the contribution of caveolin‐3 (Cav‐3), a lipid‐raft scaffolding protein, to ischemic tolerance in aged myocardium. Cav‐3 expression was reduced in aged hearts. Cardiac‐specific expression of Cav‐3 improved ischemic tolerance in both young (3 months) and aged (24 months) hearts. Aged WT hearts exhibited significant dysfunction, recovering only 20–25% of force and exhibiting almost 2‐fold higher diastolic pressure. Overexpression of Cav‐3 profoundly improved outcome in aged hearts with 60–65% recovery of pressure development and end diastolic pressure in the normal range. These data reveal a parallel decline in cardiac ischemic tolerance and Cav‐3 expression, and indicate that increasing Cav‐3 expression can eliminate age‐related ischemic intolerance. Cav‐3 may serve as a novel therapeutic target to limit dysfunction associated with cardiac aging.

Age- and Sex-Dependent Caveolar Gene Expression in Normoxic and Post-Ischemic Mouse Hearts

“…As many protective stimuli or interventions are reliant on caveolae, unraveling mechanisms governing the age-dependencies of caveolin, cavin and Popdc transcription and expression may facilitate targeted modulation of this important system. For example, intracoronary adenoviral Cav3 gene delivery may be a useful experimental approach to enhancing resistance to the damaging impacts of ischemic heart disease, as it has been shown to markedly improve caveolae formation and recovery in the aged heart (Kidd et al, 2010). Similarly, a recent preliminary study has shown that adeno-associated virus delivery of Cavin1 can enhance the expression of Cav1 , Cav3 , Cavin1 and Cavin2 transcripts (Russell et al, 2021) which showed age-related changes in this study.…”