Tan Yuxiao, Martin Thomas G, Peter Angela K, Ozeroff Christopher D, Ebmeier Christopher C, Doptis Ryan, Harrison Brooke, Leinwand Leslie A
BioFrontiers Institute, University of Colorado Boulder; Boulder, CO 80303, USA.
Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder; Boulder, CO 80309, USA.
bioRxiv. 2025 May 19:2025.05.19.654898. doi: 10.1101/2025.05.19.654898.
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.
心肌细胞增生是胎儿心脏生长的主要形式，而在大多数物种的成体中，这种增殖能力大多丧失。成体心肌细胞重新进入细胞周期的能力有限，是心脏损伤导致发病和死亡的主要原因。在此，我们报告餐后缅甸蟒心肌细胞会激活细胞周期重新进入，以促进心脏持续生长。缅甸蟒通常不常进食大餐，会导致可逆性心脏肥大。我们发现频繁投喂大餐会放大在不频繁投喂间隔中观察到的适度餐后心脏增殖。通过激活E2F和叉头框M1（FoxM1）促增殖转录网络，频繁进食的缅甸蟒会引发心肌细胞增生。这些发现表明增生是缅甸蟒心脏持续生长的自然方式，并支持将蟒蛇作为研究增殖性心脏重塑的新模型。
