Department of Anatomy, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India.
Department of Obstetrics and Gynecology, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India.
J Clin Lab Anal. 2016 Jan;30(1):75-83. doi: 10.1002/jcla.21819. Epub 2014 Dec 26.
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.
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).
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).
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.
子痫前期的病理生理学在全球范围内尚未得到明确阐明。缺氧诱导因子 1α(HIF-1α)被认为是子痫前期缺氧环境的初步因素,导致血管生成蛋白表达失衡。一种促血管生成蛋白——胎盘生长因子(PIGF)被报道在子痫前期失调。因此,本研究专注于研究子痫前期条件下的 HIF-1α 和 PIGF 及其之间可能的分子关联。
收集子痫前期患者和健康对照组的胎盘组织(n=45+45)和血清样本(n=80+80),并通过免疫组织化学和酶联免疫吸附试验(ELISA)分析 HIF-1α 和 PIGF。
在子痫前期组中,合体滋养层中明显存在 HIF-1α 的核和细胞质表达(P=0.0001),而在对照组胎盘,其定位于细胞质(P=0.0001)。与对照组相比,子痫前期患者合体滋养层细胞质中的 PIGF 表达强度较低(P=0.0001)。此外,子痫前期妇女血清中 HIF-1α 的浓度显著上调,而 PIGF 的浓度下调(P=0.0001)。因此,在组织和血清水平上均观察到 HIF-1α 和 PIGF 之间存在显著的直接负相关(P<0.01)。
血清和胎盘组织中 HIF-1α 和 PIGF 之间的直接负相关可能导致低氧化应激和内皮功能障碍,从而导致子痫前期的发病机制。