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. Author manuscript; available in PMC: 2016 Feb 3.
Published in final edited form as: Cell Metab. 2015 Feb 3;21(2):227–236. doi: 10.1016/j.cmet.2015.01.014

Figure 2. Responses of the heart to exercise.

Figure 2

(A) Organ-level responses of the heart to exercise. Exercise stimulates increases in heart size, resistance to and recovery from injury, vascularization, and output. (B) Cellular responses to exercise. Exercise stimulates cardiomyocyte hypertrophy, increases mitochondrial biosynthesis, calcium sensitivity, and contractility, and may drive cardiomyocyte proliferation. (C) Signaling pathways involved in the cardiac exercise response. 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 serum response factor to bind target gene promoters, 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. AMPK indicates AMP-activated kinase; β3-AR, β3 adrenergic receptor; C/EBPβ, CCAAT/enhancer binding protein β; Cited4, cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 4; eNOS, endothelial nitric oxide synthase; IGF-1, insulin-like growth factor-1; NO, nitric oxide; Nrg1, neuregulin1; PGC-1 α, peroxisome proliferator activated receptor gamma co-activator 1α; PI3K, phosphoinositide-3 kinase; Sirt1, Sirtuin 1; SRF, serum response factor.