Document Type
Article
Publication Date
3-11-2025
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.
Recommended Citation
Amirrad, F., La, V., Ohadi, S. et al. PGRMC2 is a pressure-volume regulator critical for myocardial responses to stress in mice. Nat Commun 16, 2422 (2025). https://doi.org/10.1038/s41467-025-57707-8
Supplementary Information
41467_2025_57707_MOESM2_ESM.pdf (12632 kB)
Peer Review File
41467_2025_57707_MOESM3_ESM.pdf (84 kB)
Description of Additional Supplementary Files
41467_2025_57707_MOESM4_ESM.mp4 (384 kB)
Supplementary Movie 1
41467_2025_57707_MOESM5_ESM.pdf (2199 kB)
Reporting Summary
41467_2025_57707_MOESM6_ESM.xlsx (29675 kB)
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The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
This article was originally published in Nature Communications, volume 16, in 2025. https://doi.org/10.1038/s41467-025-57707-8