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

Author

Listed:
  • Farideh Amirrad

    (Chapman University
    Marshall B. Ketchum University)

  • Vivian La

    (Chapman University)

  • Sharareh Ohadi

    (Chapman University)

  • Miram Albotaif

    (Chapman University)

  • Sha Webster

    (Chapman University)

  • James K. Pru

    (University of Wyoming)

  • Kiumars Shamloo

    (Chapman University)

  • Ashraf M. Mohieldin

    (Chapman University
    California Northstate University)

  • Surya M. Nauli

    (Chapman University
    University of California)

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.

Suggested Citation

  • Farideh Amirrad & Vivian La & Sharareh Ohadi & Miram Albotaif & Sha Webster & James K. Pru & Kiumars Shamloo & Ashraf M. Mohieldin & Surya M. Nauli, 2025. "PGRMC2 is a pressure-volume regulator critical for myocardial responses to stress in mice," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57707-8
    DOI: 10.1038/s41467-025-57707-8
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    References listed on IDEAS

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    1. Andrea Galmozzi & Bernard P. Kok & Arthur S. Kim & J. Rafael Montenegro-Burke & Jae Y. Lee & Roberto Spreafico & Sarah Mosure & Verena Albert & Rigo Cintron-Colon & Cristina Godio & William R. Webb & , 2019. "PGRMC2 is an intracellular haem chaperone critical for adipocyte function," Nature, Nature, vol. 576(7785), pages 138-142, December.
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