Abstract 15648: Expression of Cavoelin-3 Improves Mitochondrial Function Aad Reduces Oxidative Stress in Heart Failure
Mitochondrial dysfunction is a critical element of heart failure progression. Caveolins have been found in mitochondria, however the role of caveolins and their effects on mitochondrial function in the setting of heart failure have not been investigated. We tested if the resistance to transverse aortic constriction (TAC) induced heart failure in cardiac myocyte specific caveolin-3 overexpressing (Cav-3 OE) mice is associated with improved mitochondrial function. Cav-3 OE mice and transgene negative (TGneg) littermate controls were subjected to mitochondrial functional assays without and after 4wks of TAC. Mitochondria were isolated from TGneg and Cav-3 OE hearts with and without TAC and calcium tolerance assays, mitochondrial respiratory function assays and electron paramagnetic resonance (EPR) spectroscopy to assess oxidative stress were performed. Without TAC, immunoblotting showed increased amounts of Cav-3 within mitochondria from Cav-3 OE mice compared to TGneg mice. Mitochondria from Cav-3 OE hearts showed resistance to calcium swelling and enhanced State 3 and complex IV activity when compared to TGneg mice. EPR spectroscopy showed reduced generation of reactive oxygen species from mitochondria of Cav-3 OE mice compared to TGneg mice. After TAC, mitochondria from Cav-3OE mouse hearts showed resistance to calcium-induced swelling, greater oxygen utilization during active and resting respiratory states and reduced superoxide radical generation from mitochondria when compared to TGneg mice. These data suggest that Cav-3 OE mice have improved mitochondrial respiratory function and reduced cardiac oxidative stress after TAC and that targeted Cav-3 expression is a potentially viable strategy to rescue heart failure.
- Heart failure
- Mitochondrial energetics, heart failure, arrhythmias
- Reactive oxygen intermediates
- Oxidative stress
- © 2012 by American Heart Association, Inc.