Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 2, Pages 612-617Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0606663104
Keywords
heart failure; signal transduction; heart growth; athlete's heart
Categories
Funding
- NHLBI NIH HHS [R01 HL65742, R01 HL065742] Funding Source: Medline
- NICHD NIH HHS [K12-HD001487, K12 HD001487] Funding Source: Medline
Ask authors/readers for more resources
Physical activity protects against cardiovascular disease, and physiological cardiac hypertrophy associated with regular exercise is usually beneficial, in marked contrast to pathological hypertrophy associated with disease. The p110 alpha isoform of phosphoinositide 3-kinase (PI3K) plays a critical role in the induction of exercise-induced hypertrophy. Whether it or other genes activated in the athlete's heart might have an impact on cardiac function and survival in a setting of heart failure is unknown. To examine whether progressive exercise training and PI3K(p110 alpha) activity affect survival and/or cardiac function in two models of heart disease, we subjected a transgenic mouse model of dilated cardiomyopathy (DCM) to swim training, genetically crossed cardiac-specific transgenic mice with increased or decreased PI3K(p110 alpha) activity to the DCM model, and subjected PI3K(p110 alpha) transgenics to acute pressure overload (ascending aortic constriction). Life span, cardiac function, and molecular markers of pathological hypertrophy were examined. Exercise training and increased cardiac PI3K(p110 alpha) activity prolonged survival in the DCM model by 15-20%. In contrast, reduced PI3K(p110 alpha) activity drastically shortened lifespan by approximate to 50%. Increased PI3K(p110 alpha) activity had a favorable effect on cardiac function and fibrosis in the pressure-overload model and attenuated pathological growth. PI3K(p110 alpha) signaling negatively regulated G protein-coupled receptor stimulated extracellular responsive kinase and Akt (via PI3K, p110 gamma) activation in isolated cardiomyocytes. These findings suggest that exercise and enhanced PI3K(p110 alpha) activity delay or prevent progression of heart disease, and that supraphysiologic activity can be beneficial. Identification of genes important for hypertrophy in the athlete's heart could offer new strategies for treating heart failure.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available