Figure 2.

Mechanisms underlying modulation of HER2-directed therapy cardiotoxicity through aerobic exercise. Aerobic exercise induces cardioprotection via upregulation of Nrg1 synthesis and release, thus activating pathways A–C; inhibition of TGF-β1 and C/EBPβ signaling and upregulation of GATA4 (pathway D); and activation of AMPK expression (pathway E).

Abbreviations: AMPK, AMP-activated protein kinase; C/EBPβ, CCAAT/enhancer binding protein; Fak, focal adhesion kinase; MAPK, mitogen-activated protein kinase; Nrg1, Neuregulin-1β; PI3K, phosphatidylinositol 3-kinase; Smad, small mother against decapentaplegic; TGFβ, transforming growth factor β.