PPARGC1A and cardiac hypertrophy: When exposed to overload, activated intracellular hypertrophic signaling pathways facilitate myocardial angiogenesis to dissolve the hypoxic situation and to maintain cardiac contractile function, but sustained overload induces pathological hypertrophy, generally progressing to HF.368,369 Growing compelling evidence suggested that PGC-1α is a multifaceted regulator in both physiological and pathological forms of myocardial hypertrophy.