Is Atrial Natriuretic Peptide (ANP) and Natriuretic Peptide Receptor-A (NPR-A) Expression in Human Placenta and Decidua Normal?

Abstract

Background Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates blood pressure and the salt-water balance in the blood. It acts through natriuretic peptide receptors (NPR), and the major biologically active ANP receptor is natriuretic peptide receptor-A (NPR-A). Aberrant forms of ANP and its receptors have been reported in patients with preeclampsia. However, whether aberrant forms of ANP or NPR-A are present in preeclamptic placenta, and what their role is in preeclampsia pathogenesis, has not yet been elucidated clearly. The aim of this study was to assess the expression of ANP and NPR-A in the placenta and decidua and its role in preeclampsia development. Material/Methods The expression of ANP and NPR-A in the first-trimester villous and decidua, full-term placenta, and preeclamptic placenta was determined using immunohistochemistry and Western blot analysis. The HTR8/SVneo cell line was used to investigate the role of NPR-A in proliferation, apoptosis, and invasion using Cell Counting Kit-8 analysis, flow cytometry analysis, and a Transwell invasion assay, respectively. Results ANP and NPR-A were localized in the syncytiotrophoblasts, cytotrophoblasts, and trophoblast columns of human first-trimester villous trophoblast cells of decidua, and in the glandular epithelium and extravillous trophoblast cells of decidua. ANP-positive and NPR-A-positive cells in the decidual stroma were clustered around and infiltrated into the vascular wall of the spiral artery undergoing remodeling. NPR-A expression was significantly reduced in preeclamptic placentas, and NPR-A knockdown significantly impaired the invasion ability of HTR8/SVneo cells, although it had no effect on cell proliferation and apoptosis. Conclusions ANP and NPR-A are involved in human placental development. Decreased levels of NPR-A may contribute to the development of preeclampsia.

ANP rescues the preeclamptic symptoms inAxlknockout mice by improving trophoblast function ANP rescues the preeclamptic symptoms

“…ANP has been shown to facilitate trophoblast cell invasion in vitro (Cui et al, 2012, Wang, Wang et al, 2020. In HTR8/SVneo cells, a cell line of human invasive cytotrophoblasts, knockdown of the ANP receptor, NPR-A with siRNA impaired its invasive ability, but had no effect on its proliferation or frequency of apoptosis (Tan, Lin et al, 2019). These findings are concordant with our was not certified by peer review) is the author/funder.…”

Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia

“…Gene expression is a more specific way to analyze the potential expression of ANP protein in non-cardiac tissues. In humans, NPPA mRNA has been detected in the non-pregnant uterus [71] and in myometrial cells, decidual cells, and trophoblasts of the pregnant uterus [72,73]. Similar uterine Nppa mRNA expression has been found in rodents [16,74,75].…”

“…In supporting this hypothesis, the ANP re NPR-A is expressed in human trophoblasts and decidual stromal cells [16,71]. In cu human trophoblasts, ANP treatment increases intracellular cGMP levels and pro trophoblast invasion in Matrigel assays, whereas NPR-A knockdown suppresses t blast invasion [16,73,134]. Moreover, markedly decreased placental corin and NPR pression and increased levels of pro-ANP are found in preeclamptic women [7 These results indicate that ANP-mediated signaling probably has a role in prom trophoblast invasion, and that defects in ANP signaling may contribute to uterine placental pathology in preeclampsia.…”

“…In supporting this hypothesis, the ANP receptor NPR-A is expressed in human trophoblasts and decidual stromal cells [16,71]. In cultured human trophoblasts, ANP treatment increases intracellular cGMP levels and promotes trophoblast invasion in Matrigel assays, whereas NPR-A knockdown suppresses trophoblast invasion [16,73,134]. Moreover, markedly decreased placental corin and NPR-A expression and increased levels of pro-ANP are found in preeclamptic women [73,134].…”

ANP promotes HTR‐8/SVneo cell invasion by upregulating protein kinase N 3 via autophagy inhibition

“…In addition, the decreased expression of CORIN was detected in preeclamptic placenta, with an accumulation of inactive form pro‐ANP compared with that of normal pregnancies 6 . Moreover, ANP receptor NPR‐A was reduced in the preeclamptic placenta 11 and maternal vessel endothelium from preeclamptic patients 12 . Although growing evidence has confirmed the importance of active ANP in regulating trophoblast cell function in preeclampsia pathogenesis, none focuses on the underlying mechanisms and active molecules.…”