FoxO1 is required for physiological cardiac hypertrophy induced by exercise but not by constitutively active PI3K.

FoxO1 is required for physiological cardiac hypertrophy induced by exercise but not by constitutively active PI3K. Am J Physiol Heart Circ Physiol. 2021 Feb 12;: Authors: Weeks KL, Tham YK, Yildiz SG, Alexander Y, Donner DG, Kiriazis H, Harmawan CA, Hsu AT, Bernardo BC, Matsumoto A, DePinho RA, Abel ED, Woodcock EA, McMullen JR Abstract The insulin-like growth factor 1 receptor (IGF1R) and phosphoinositide 3-kinase p110a (PI3K) are critical regulators of exercise-induced physiological cardiac hypertrophy, and provide protection in experimental models of pathological remodeling and heart failure. Forkhead box class O1 (FoxO1) is a transcription factor which regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K activation in vitro, but its role in physiological hypertrophy in vivo was unknown. We generated cardiomyocyte-specific FoxO1 knockout (cKO) mice and assessed the phenotype under basal conditions and settings of physiological hypertrophy induced by 1) swim training, or 2) cardiac-specific transgenic expression of constitutively active PI3K (caPI3KTg+). Under basal conditions, male and female cKO mice displayed mild interstitial fibrosis compared with control (CON) littermates, but no other signs of cardiac pathology were present. In response to exercise training, female CON mice displayed an increase (~21%) in heart weight normalized to tibia length vs untrained mice. Exercise-induced hypertrophy was blunted in cKO mice. ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research