| 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. |
| Authors |
Farideh Amirrad  , Vivian La , Sharareh Ohadi , Miram Albotaif , Sha Webster , James K. Pru  , Kiumars Shamloo , Ashraf M. Mohieldin , Rajasekharreddy Pala
|
| Journal Info |
Nature Portfolio | Nature Communications , vol: 16
, iss: 1
|
| Publication Date |
3/11/2025 |
| ISSN |
2041-1723 |
Type |
article |
| Open Access |
gold
|
| DOI |
https://doi.org/10.1038/s41467-025-57707-8 |
| Keywords |
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