HIF-1 Alpha and Placental Growth Factor in Pregnancies Complicated With Preeclampsia: A Qualitative and Quantitative Analysis - PubMed (original) (raw)

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

Gayatri Rath et al. J Clin Lab Anal. 2016 Jan.

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.

Keywords: HIF-1α; PIGF; hypoxia; preeclampsia.

© 2014 Wiley Periodicals, Inc.

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Figures

Figure 1

Figure 1

(A) Control placenta (40 weeks) showing moderate cytoplasmic expression of HIF‐1α in syncytiotrophoblast; (B and C) preeclamptic placenta (38 and 36 weeks) showing nuclear accumulation of HIF‐1α in syncytiotrophoblast; (D) control placenta (32 weeks) showing moderate cytoplasmic expression of PIGF in syncytiotrophoblast; (E) preeclamptic placenta (32 weeks) showing mild cytoplasmic expression of PIGF in syncytiotrophoblast; (F) negative control incubated with IgG showing placental villi. Arrow shows the expression of protein. Magnification: 400×.

Figure 2

Figure 2

Comparison of immunohistochemical _H_‐score analysis. (A) HIF‐1α expression in cytoplasm and nucleus of syncytiotrophoblast cells of control and preeclamptic patients. (B) PIGF expression in cytoplasm of syncytiotrophoblast cells of control and preeclamptic group.

Figure 3

Figure 3

ROCs curve showing the expression of HIF‐1α and PIGF to differentiate preeclamptic group from control. (A) HIF‐1α (AUC = 0.989, sensitivity = 88.9%, specificity = 88.9%). (B) PIGF (AUC = 0.962, Sensitivity = 82.2%, specificity = 82.2%).

Figure 4

Figure 4

Box plot showing the serum concentration (pg/ml) of (A) HIF‐1α and (B) PIGF in control and preeclamptic patients. The solid bar indicates median, upper, and lower limits of box, 75th and 25th percentiles; upper and lower bars, maximum and minimum values (P < 0.05).

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