Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy.

Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Research Abstract Details 

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Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Abstract Text:

Julie R McMullen,Fatemeh Amirahmadi,Elizabeth A Woodcock,Martina Schinke-Braun,Russell D Bouwman,Kimberly A Hewitt,Janelle P Mollica,Li Zhang,Yunyu Zhang,Tetsuo Shioi,Antje Buerger,Seigo Izumo,Patrick Y Jay,Garry L Jennings,

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 p110alpha 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(p110alpha) 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(p110alpha) activity to the DCM model, and subjected PI3K(p110alpha) 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(p110alpha) activity prolonged survival in the DCM model by 15-20%. In contrast, reduced PI3K(p110alpha) activity drastically shortened lifespan by approximately 50%. Increased PI3K(p110alpha) activity had a favorable effect on cardiac function and fibrosis in the pressure-overload model and attenuated pathological growth. PI3K(p110alpha) signaling negatively regulated G protein-coupled receptor stimulated extracellular responsive kinase and Akt (via PI3K, p110gamma) activation in isolated cardiomyocytes. These findings suggest that exercise and enhanced PI3K(p110alpha) 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.

Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Publishing Authors By Initials

JR McMullen,F Amirahmadi,EA Woodcock,M Schinke-Braun,RD Bouwman,KA Hewitt,JP Mollica,L Zhang,Y Zhang,T Shioi,A Buerger,S Izumo,PY Jay,GL Jennings,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 612-7

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 3

MONTH: 01

YEAR: 2007

Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: physiology

Chemical & Substance for Abstract: Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Information

Substance Name: 1-Phosphatidylinositol 3-Kinase

Registry Number: EC 2.7.1.137

Grant and Affiliation Information for Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy.

AFFILIATION: Experimental Cardiology and Heart Failure Division, Baker Heart Research Institute, Melbourne 8008, Australia. julie.mcmullen@baker.edu.au

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL65742

ACRONYM: HL

MEDLINETA: Proc Natl Acad Sci U S A

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