Work

PGRMC2 is a pressure-volume regulator critical for myocardial responses to stress in mice

Year: 2025

Type: article

Abstract: Progesterone receptors are classified into nuclear and membrane-bound receptor families. Previous unbiased proteomic studies indicate a potential association between cardiac diseases and the progesterone receptor membrane-bound component-2 (PGRMC2); however, the role of PGRMC2 in the heart remains unknown. In this study, we use a heart-specific knockout (KO) mouse model (MyH6•Pgrmc2flox/flox) in which the Pgrmc2 gene was selectively deleted in cardiomyocytes. Here we show that PGRMC2 serves as a mediator of steroid hormones for rapid calcium signaling in cardiomyocytes to maintain cardiac contraction, sufficient stroke volume, and adequate cardiac output by regulating the cardiac pressure-volume relationship. The KO hearts from male and female mice exhibit an impairment in pressure-volume relationship. Under hypoxic conditions, this pressure-volume dysregulation progresses to congestive left and right ventricular failure in the KO hearts. Overall, we propose that PGRMC2 is a cardiac pressure-volume regulator to maintain normal cardiac physiology, especially during hypoxic stress. PGRMC2 is a membrane-bound progesterone receptor crucial for fast-signaling responses. Here, the authors shows that PGRMC2 regulates cardiac pressure-volume relationships and mediates steroid hormone signaling to maintain calcium homeostasis, ensuring proper heart contraction and function under stress.

Source: Nature Communications

DOI: 10.1038/s41467-025-57707-8