Levels and Significance of Arachidonic Acid Metabolites in Hypertensive Disorders of Pregnancy: A Prospective Cohort Study

Abstract

Background: This project aimed to investigate the role of two arachidonic acid metabolites (14,15-epoxyeicosatrienoic acid (14,15-EET) and 15-hydroxyeicosateraenoic acid (15-HETE)) as a precursor of hypertensive disorders in pregnancy by comparing their serum levels between third-trimester hypertensive and normal pregnant women. The relationship between their differential levels and pregnancy outcomes was investigated to clarify the role of arachidonic acid metabolites in the occurrence and development of hypertensive disorders during pregnancy. Methods: This is a prospective cohort study and a total of 88 patients were included in the study. 17 of them were recognized as the gestational hypertension and 25 of them were considered to be the preeclampsia. 24 women were diagnosed with severe preeclampsia. The control group consisted of 22 healthy patients pregnancy course, with no disease at the present and in the history. For this purpose, the serum levels of 14,15-EET and 15-HETE of gestational hypertension, preeclampsia (PE) and normal pregnant women group were detected by enzyme-linked immunosorbent assay (ELISA) during the third trimester of pregnancy. It was followed by detecting placental cytochrome P450 2J2 (CYP2J2) and 15-lipoxygenase-2 (15-LOX-2) expression and localization using immunohistochemistry, their corresponding proteins employing western blotting. All outcomes of maternal pregnancy were then statistically analyzed. Results: The analysis indicated that the levels of 14,15-EET, and 15-HETE were significantly higher (p < 0.05) in gestational hypertension compared to control, where the same differences were observed when severe preeclampsia and preeclampsia groups were compared, which were altogether higher than gestational hypertension group patients. Similarly, the 14,15-EET and 15-HETE levels were significantly (p < 0.05) higher in the adverse pregnancy outcome than in the normal pregnancy outcome group in severe preeclampsia. The immunohistochemical analysis results revealed that the positive staining for CYP2J2 and 15-LOX-2 expression in the placenta of the preeclampsia group was significant (p < 0.05) compared to the normal pregnant control and gestational hypertension groups, with significantly higher (p < 0.05) relative CYP2J2 and 15-LOX-2 protein levels in preeclampsia compared to normal control pregnancy group. Conclusions: The study concluded that the 14,15-EET and 15-HETE might be involved in gestational hypertension pathophysiology and preeclampsia, associated with disease severity and adverse pregnancy outcomes. Moreover, CYP2J2 and 15-LOX-2 signaling expression in the placenta may be related to arachidonic acid metabolites generated in preeclampsia.

Keywords

• 14,15-eet
• 15-hete
• arachidonic acid metabolites
• gestational hypertension
• preeclampsia