Abstract P614: Renin Angiotensin System: A Placental Perspective

Abstract

Renin Angiotensin System (RAS) is a major physiological regulator of Blood Pressure. In pregnancy the placental RAS plays a critical role in maintaining utero-placental blood circulation, necessary for proper fetal development. Proteinuria, a clinical implication of renal injury, is common in hypertensive disorders of pregnancy, including Preeclampsia. In the present study we tried to study whether Proteinuria is a manifestation of the RAS components in placenta. Placenta, collected from the pregnant women was divided in two categories- those having proteinuria and those not. The levels of the Ang II type 1 receptor (AT1), Ang II type 2 receptor (AT2) and ACE2 genes was determined by semi-quantitaive PCR while the Immunoblotting procedure was used to determine the protein levels of the AT1 and AT2 receptors, in the placenta of women of both categories. All the values were normalized with β-actin, used as an internal control. The AT1R gene expression was significantly decreased in the placenta of women exhibiting proteinuria compared to those that did not (0.694±0.116, n=7 vs. 1.250±0.176,n=9 p<0.05), while the levels of AT2R gene expression also showed the same trend (0.9571±0.2206,n=7 vs. 1.960±0.329,n=9,p<0.05). Similarly the levels of ACE2 gene too was significantly decreased in placenta exhibiting proteinuria compared to those which did not exhibit proteinuria (0.2775 ± 0.05747, n=6 vs. 0.2343 ± 0.02277, n=7, p<0.05). The Immuno-blot analysis demonstrated that the levels of AT1R protein were significantly up-regulated in the placenta of the women exhibiting proteinuria compared to those that did not (0.600±0.125,n=5 vs. 0.330±0.046,n=8, p< 0.05), while the levels of AT2R protein was significantly decreased in the placenta of women exhibiting proteinuria compared to those that did not (0.493±0.028, n=5 vs. 0.9963±0.163,n=8, p< 0.05). A differential pattern of the receptor types of Ang II seems to be related with the presence of Proteinuria. The increased AT1 receptor protein function could be accounting for inducing mediators that cause Proteinuria. The effects of AT2 receptor Protein and gene and the ACE2 gene, having a protective role, needs to be elucidated further for mechanistic insights on the actual relationship between the RAS components.