IGF1 and cardiac hypertrophy: It has been known that angiotensin II (Ang II), endothelin-1 (ET-1), norepinephrine, and their downstream signaling pathways (e.g., calcineurin, mitogen-activated protein kinase (MAPK), and calmodulin) contribute to the development of pathological cardiac hypertrophy.48,53 While the insulin growth factor-1/phosphoinositide-3 kinase/protein kinase B (IGF1/PI3K/Akt) pathway and the transcription factor CCAAT/enhancer binding protein β (C/EBPβ)/CITED4 pathway are canonical signaling pathways that have been well described for exercise-induced physiological cardiac hypertrophy.