Dynamic cardiac hyperplasia and hypertrophy in Burmese pythons

Cardiomyocyte hyperplasia is the primary form of fetal heart growth, whereas this proliferative capacity is largely lost in adults across most mammalian 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 postprandial Burmese python cardiomyocytes activate cell cycle re-entry to promote persistent cardiac growth. Burmese pythons normally eat large meals infrequently, resulting in reversible cardiomyocyte hypertrophy. We found that frequent feeding of large meals amplifies the modest postprandial cardiac proliferation identified in an infrequent feeding interval. By activating E2F and Forkhead Box M1 (FOXM1) pro-proliferation transcriptional networks, frequently fed Burmese pythons potentiate cardiomyocyte proliferation in addition to transient cardiac myocyte hypertrophy. These findings identify hyperplasia as a natural means of sustained cardiac growth in Burmese pythons and demonstrate the use of pythons as a model for investigating noninjury-induced proliferative cardiac remodeling.NEW & NOTEWORTHY This study shows that adult Burmese pythons can not only undergo reversible cardiomyocyte hypertrophy after feeding but can also activate cardiomyocyte cell-cycle re-entry and achieve hyperplasia, especially with frequent large meal consumption. Frequent feeding amplifies proliferation by engaging E2F and FOXM1 pro-proliferative signaling, resulting in sustained heart growth through hyperplasia in adult python hearts. These findings establish Burmese pythons as a new model for proliferative cardiac remodeling with potential insights into adult heart regenerative biology.