Impact of ACE2 and TMPRSS2 Expression in Patients with Preeclampsia

Abstract

Background/Aim: As maternal morbidity and mortality during pregnancy have increased during the COVID-19 pandemic, studies on pregnancy-related complications from SARS-CoV-2 infection are being actively conducted. Considering that pregnant women with COVID-19 may develop a preeclampsia (PE)-like syndrome, it is necessary to differentiate it from PE because true PE can result in an unfavorable perinatal outcome during a hasty delivery. Materials and Methods: We investigated the protein expression of transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) in placental samples from 42 normotensive (n=9) and PE (n=33) patients without SARS-CoV-2 infection. We isolated placental trophoblast cells from normotensive and PE patients without evidence of SARS-CoV-2 infection to determine the mRNA and protein expression levels of TMPRSS2 and ACE2. Results: High ACE2 cytoplasmic expression in extravillous trophoblasts (EVTs) was correlated with lower fibrin deposition (p=0.017). In comparison with high nuclear TMPRSS2 expression, low nuclearTMPRSS2 expression in endothelial cells (ECs) was positively correlated with PE (p=0.005), significantly higher systolic blood pressure (p=0.006), and higher urine protein-to-creatinine ratio (p=0.022). In contrast, high cytoplasmic TMPRSS2 expression in fibroblasts (FBs) was correlated with higher urine protein-to-creatinine ratio (p=0.018). Trophoblast cells extracted from PE placental tissue showed lower mRNA levels for both ACE2 and TMPRSS2. Conclusion: TMPRSS2 nuclear expression in ECs and cytoplasmic expression in FBs of the placenta may be related to a trophoblast-independent PE mechanism, and TMPRSS2 could be a new biomarker to discriminate actual PE from a PE-like syndrome associated with COVID-19.