Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia

Figures

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  Figure 1. Corin-mediated pro-ANP processing in cardiomyocytes. Corin is a type II transmembrane serine protease anchoring on the cell surface. In cardiomyocytes, pro-ANP is stored in the dense granules. Upon stimulation, pro-ANP is secreted from cardiomyocytes and cleaved by corin, generating biologically active ANP.

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  Figure 2. Illustration of endometrial decidualization, vascular remodeling, and trophoblast invasion in non-pregnant and pregnant uteruses. In the non-pregnant uterus, endometrial decidualization and vascular remodeling occur in the secretory phase of the menstrual cycle after ovulation. In the pregnant uterus, endometrial decidualization and vascular remodeling are accelerated upon embryo implantation, which facilitates trophoblast invasion. The invading trophoblasts in turn stimulate endometrial decidualization and vascular remodeling in a reciprocal manner.

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  Figure 3. A model of ANP function in endometrial decidualization and spiral artery remodeling in the pregnant uterus. In the pregnant uterus, ANP stimulates stromal cell decidualization and TNF-related apoptosis-inducing ligand (TRAIL) expression and secretion, inducing apoptosis in arterial smooth muscle cells (SMCs). Apoptotic SMCs release cyclophilin B (CyPB) to upregulate TRAIL receptor (TRAILR) expression in endothelial cells (ECs), making the cells susceptible to TRAIL-mediated apoptosis. The sequential death in SMCs and ECs facilitates spiral artery remodeling.

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  Figure 4. A model of ANP signaling in placental trophoblasts. ANP activates natriuretic peptide receptor A (NPR-A) to enhance adenosine 5′-monophosphate-activated protein kinase (AMPK) and the mammalian target of rapamycin complex 1 (mTORC1) signaling, leading to autophagy inhibition and protein kinase N3 (PKN3) upregulation, thereby increasing trophoblast invasiveness.