This recent study published in Science Advances provides new insights into the role of Prothymosin alpha (PTMA) in cardiac biology. The authors demonstrate that PTMA acts as a key regulator of cardiomyocyte proliferation by modulating the cell cycle. Using both in vitro and in vivo models, the study shows that overexpression of PTMA in cardiomyocytes enhances proliferation and contributes to improved cardiac repair following injury.

Although PTMA had previously been implicated in cardiac regeneration and repair (PMID: 36125329, PMID: 33398012), this study provides additional evidence supporting its pro-regenerative role.
The authors overexpressed PTMA in rodent cardiomyocytes, which increased the cell cycle activity measured by EdU, Ki67 and pH3, both in vitro and in vivo. Additionally, in a mouse model of myocardial infarction, PTMA gene therapy improved cardiac function and reduced scar size.

Given the limited regenerative capacity of adult mammalian hearts, identifying factors like PTMA that can stimulate cardiomyocyte renewal is of great therapeutic interest. Notably, the in vivo data suggest that PTMA has functional relevance beyond the cellular level, translating to improved cardiac performance post-injury.
Still, some critical questions need to be answered. For instance, although the authors observed cardiomyocyte proliferation, the study did not assess whether newly formed cardiomyocytes are functionally integrated into the myocardium or whether they mature properly. We know from previous research that simply increasing the number of cardiomyocytes does not guarantee improved cardiac function unless those cells are electrically and mechanically integrated.

Despite this limitation, the study adds to the growing body of research focused on promoting heart regeneration and opens the door to potential gene- or protein-based therapies aimed at boosting endogenous repair mechanisms.