Abstract 12340: Exercise-Induced Cardiac Protection is Regulated by Phosphoinositide 3-Kinase p110α, Independently of Heat Shock Protein 70
Signaling mechanisms that mediate exercise-induced cardiac protection remain unclear. Phosphoinositide 3-kinase p110α (PI3K) is a lipid kinase which is activated in cardiomyocytes during exercise and is critical for heart growth following long-term training. We hypothesized that PI3K is critical for exercise-induced protection of the heart and acts, at least in part, via the cardioprotective molecular chaperone heat shock protein 70 (Hsp70). Cardiac-specific transgenic mice with elevated or reduced PI3K activity (caPI3K and dnPI3K mice, respectively) and non-transgenic controls were subjected to 4 weeks of swim training (90 minute sessions, twice daily) followed by 1 week of pressure overload induced by ascending aortic banding (n=4-9 per group). Aortic banding was also performed on caPI3K mice deficient for Hsp70 (caPI3K-Hsp70 KO mice; n=3) and dnPI3K mice overexpressing Hsp70 (dnPI3K-Hsp70 Tg mice; n=6) to determine whether Hsp70 plays a role in PI3K-mediated cardiac protection. Echocardiography was used to assess cardiac function. Exercise training protected non-transgenic mice from developing heart failure following aortic banding (better systolic function and less cardiac hypertrophy, lung congestion and left ventricular (LV) fibrosis (P<0.05) than non-swim controls; see table). Banded caPI3K mice were protected from developing heart failure regardless of whether or not mice were exercised prior to banding (see table). In contrast, exercise training had no protective effect in banded dnPI3K mice (worse systolic function, lung congestion and LV fibrosis (P<0.05) compared with non-transgenic; see table). Transgenic overexpression of Hsp70 did not improve the cardiac phenotype of banded dnPI3K mice, and loss of Hsp70 did not abolish the protection observed in caPI3K mice. In conclusion, PI3K is critical for mediating the protective effects of long-term exercise training in a mouse model of pressure overload and acts independently of Hsp70.
- © 2011 by American Heart Association, Inc.