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Review
. 2012 Nov 27;126(22):2625-35.
doi: 10.1161/CIRCULATIONAHA.111.060376.

Can exercise teach us how to treat heart disease?

Nina Mann  1 , Anthony Rosenzweig
Affiliations
Review

Can exercise teach us how to treat heart disease?

Nina Mann et al. Circulation. .
No abstract available

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Conflict of interest statement

Disclosures and conflicts of interest: None.

Figures

Figure 1
Figure 1. Overview of the systemic and cardiac-specific effects of exercise
Endurance exercise has multiple systemic effects, ranging from increased skeletal muscle growth to vascular remodeling and improved energetics. Exercise also exerts direct effects on the heart itself, including increased cardiac growth, protection against ischemic damage, and modulation of cardiac function, metabolism, and vascular supply. (Illustration by AR)
Figure 2
Figure 2. Key signaling pathways involved in mediating exercise-induced cardiac remodeling
Exercise activates the IGF1-PI3K-Akt cascade. Signals then converge at the level of the nucleus, resulting in inhibition of the transcription factor C/EBPβ. Down-regulation of C/EPBβ, in turn, frees SRF to bind target gene promotors, contributing to activation of an “exercise gene set,” and, ultimately, cardiac growth. Meanwhile, activation of CITED4 may drive cardiomyocyte proliferation, as does signaling through Nrg1 and ErbB4. Akt also mediates angiogenesis and vascular remodeling via eNOS, and exerts beneficial metabolic effects through cross-talk with AMPK, Sirt1, and PGC-1α. In mitochondria, Sirt3, which is activated by exercise, works to protect against age-related cardiac dysfunction. Finally, exercise also modulates the secretion of circulating factors, primarily from skeletal muscle and adipocytes, such as adiponectin, myostatin (MSTN), irisin, and Fstl1.
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