The regulation of sVEGFR-2 and sVEGFR-3 in the serum of pregnant women with HIV- related Pre-eclampsia recieving antiretroviral therapy.

Abstract

Background: An imbalance in the concentration of pro- and anti-angiogenic factors is evident in preeclampsia (PE). This study evaluated the expression of soluble vascular endothelial growth factor receptor 2 (sVEGFR-2) and sVEGFR-3 in the serum of preeclamptic compared to normotensive women complicated by Human Immunodeficiency Virus (HIV) infection. Additionally, in light of the coronavirus disease 2019 (COVID-19) pandemic, maternal and foetal health is a great concern; hence, we have composed a review article that provides an insight into the synergy of PE, HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, as well as the involvement of epigenetic regulation. Method: The serum expression of sVEGFR-2 and sVEGFR-3 in preeclamptic vs normotensive pregnancies, stratified by HIV status (n = 19) was evaluated through the utilization of a Milliplex Multiplex immunoassay. Results: In comparison to normotensive (HIV-negative and HIV-positive), gestational age (p = 0.0004), systolic and diastolic blood pressure (p<0.0001) , and parity (p = 0.0042) were significantly different in preeclamptic (HIV-negative and HIV-positive) pregnancies. The serum expression of sVEGR-2 was significantly downregulated in PE compared to normotensive pregnancies (p = 0.0025), regardless of HIV status. A downward trend in the concentration of sVEGFR-3 was observed in preeclamptic women (p = 0.0586), irrespective of HIV status. Across all groups, the concentration of sVEGFR-2 was significantly downregulated in HIV-positive PE (p = 0.0053) and the expression of sVEGFR-3 was significantly reduced in HIV-negative PE (p = 0.0393), compared to HIV-negative PE. Conclusion: This novel investigation reports a significant downregulation of serum sVEGFR-2 and a downward trend in the serum expression of sVEGFR-3 in preeclamptic compared to normotensive pregnancies. The hypoxic microenvironment of PE is associated with endothelial cell damage which greatly contributes to the decreased serum expression of sVEGFR-2 and sVEGFR-3. The use of antiretroviral therapy (ART) reconstitutes the immune response in HIV-positive preeclamptic women; hence, it significantly contributes to the risk of developing PE. Furthermore, the HIV-1 trans-activator of transcription protein mimics the behaviour of vascular endothelial growth factors (VEGF) due to their structural homology; however, this does not counterbalance the decline of VEGF in PE due to the administration of ART. In addition, the association of pregnancy with an upregulation of angiotensin converting enzyme 2 receptors increases the risk of pregnant women being infected with SARS-CoV- 2. Further investigations are essential to critically evaluate the influence of HIV infection and the epigenetic regulation of these soluble anti-angiogenic factors.