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

Progesterone receptors are classified into nuclear and membrane-bound receptor families.  In this study, we evaluate the role of progesterone receptor membrane-bound component-2 (PGRMC2) in the heart. We use a heart-specific knockout (KO) mouse model (MyH6•Pgrmc2flox/flox) in which the Pgrmc2 gene was specifically 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 and support stroke volume and cardiac output by regulating the cardiac pressure-volume relationship. The KO hearts from both male and female mice exhibit impairment in regulating the pressure-volume relationship.  Under hypoxic conditions, this dysregulation in the KO hearts is subsequently progressed to congestive left and right ventricular failure.

Methods
Total mRNA transcriptome sequencing of heart samples was studied using the NovaSeq X Plus platform (Illumina).