Immunoexpression of Placental Growth Factor (PlGF) and Soluble FMS-like Tyrosine Kinase 1 (sFlt-1) in the Placental Bed of Preeclamptic women of African ancestry living with HIV infection

Abstract

Background: Preeclampsia, a serious pregnancy complication, is associated with defective placentation and adverse maternal risk. Placental Growth Factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) are pivotal in placental development and are dysregulated in preeclampsia. Women with HIV/AIDS and receiving ART may face an increased susceptibility to preeclampsia development due to immunological and angiogenic imbalance. This study utilizes morphometric image analysis to investigate the immuno-expression of PlGF and sFlt-1 in HIV-associated preeclampsia, providing insight into its underlying aetiology. Methods: Normotensive (N; n = 60) and preeclamptic (PE; n = 120) women were stratified by HIV status (HIV- and HIV+), and gestational age i.e. early onset of PE (EOPE; <34 weeks) and late onset of PE (LOPE; ≥34 weeks). Placental bed tissues were stained using conventional immunohistochemistry with mouse anti-human sFlt-1 and PlGF antibodies. Morphometric image analysis was performed using Zeiss Axio-Vision software. Results were analyzed using a Graph Pad Prism software. Results: sFlt-1 immunoreactivity showed no significant difference between preeclamptic and normotensive women (p=0.8661) but was slightly increased within the preeclamptic myometrium (20.83 ±3.134) compared to normotensive (20.67 ±3.188), irrespective of HIV status. Significant differences in sFlt-1 were noted when stratified by gestational age (p<0.0001), with higher levels in EOPE (22.27 ±2.707) compared to normotensive (20.67 ±3.188; p=0.0140) and LOPE (19.39 ±2.880; p=0.0054). PlGF immunostaining showed no significant difference overall (p=0.7387) but was decreased in PE (20.58 ±3.624) compared to normotensive (20.82 ±3.165) pregnancies. PlGF was significant increase in EOPE (21.79 ±3.54) compared to LOPE (19.37 ±3.312; p=0.0013) groups. HIV status did not significantly affect sFlt-1 or PlGF levels. Nonetheless, sFlt-1 was higher in HIV-negative (21.17 ±2.982) compared to HIV-positive (20.60 ±2.671; p=0.1411) women, and PlGF was slightly higher in HIV-positive women (20.93 ±3.827) compared to HIV-negative (20.40 ±3.072; p=0.3042). Conclusion: These findings highlight the intricate interplay of angiogenic factors in the pathophysiology of PE, suggesting potential implications for diagnostic and therapeutic strategies. Despite, sFlt-1 being up-regulated by gestational age, ARTs may be implicated in the dysregulation of these angiogenic factors due to a heightened immune milieu.