HIF-1 Alpha and Placental Growth Factor in Pregnancies Complicated With Preeclampsia: A Qualitative and Quantitative Analysis

Abstract

Background: The pathophysiology of preeclampsia is not clearly understood worldwide. Hypoxia inducible factor 1α (HIF-1α) is thought to be the preliminary factor for the hypoxic conditions prevailing in preeclampsia, which causes imbalance in the expression of angiogenic proteins. A proangiogenic protein, placental growth factor (PIGF), is reported to be dysregulated in preeclampsia. Therefore, this study focuses on the investigation of HIF-1α and PIGF in preeclamptic conditions and a possible molecular association between them. Methods: Placental tissue (n = 45 + 45) and serum samples (n = 80 + 80) of preeclamptic patients and healthy control were collected and processed for the analysis of HIF-1α and PIGF by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Results: In preeclamptic group, the significant nuclear and cytoplasmic expression of HIF-1α was noticed in syncytiotrophoblast (P = 0.0001) but in control placenta, it was localized to cytoplasm (P = 0.0001). The intensity of PIGF expression was lower in syncytiotrophoblast cytoplasm (P = 0.0001) in preeclamptic cases as compared with control. Also, the significant upregulated concentration of HIF-1α and downregulated PIGF was observed in serum samples of preeclamptic woman (P = 0.0001). Thus, there was a significant direct negative correlation between HIF-1α and PIGF both at tissue and serum level (P < 0.01). Conclusion: The direct inverse association between HIF-1α and PIGF in serum and placental tissues may be responsible for the low oxidative stress and endothelial dysfunction, leading to the pathogenesis of preeclampsia.