Dynamic hyperplastic cardiac growth in Burmese pythons

Abstract

Cardiomyocytes hyperplasia is the primary form of fetal heart growth, whereas this proliferative capacity is largely lost in adults across most species. The limited ability of adult cardiomyocytes to re-enter the cell cycle is a major cause of cardiac injury-induced morbidity and mortality. Here, we report that post-prandial Burmese python cardiomyocytes activate cell cycle re-entry to promote persistent cardiac growth. Burmese pythons normally eat large meals infrequently, resulting in reversible cardiac hypertrophy. We found that frequent feeding of large meals amplifies the modest post-prandial cardiac proliferation identified in an infrequent feeding interval. By activating E2F and Forkhead Box M1 (FoxM1) pro-proliferation transcriptional networks, frequently fed Burmese pythons initiate cardiomyocyte hyperplasia. These findings identify hyperplasia as a natural means of sustained cardiac growth in Burmese pythons and support the use of pythons as a new model for investigating proliferative cardiac remodeling.