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Cell signaling expression of stat-3 and mek-1 in HIV-associated pre-eclampsia.

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Background: Sub-Saharan Africa remains the epicenter of the HIV pandemic. In South Africa 35.8% of maternal deaths are ascribed to non-pregnancy related infections, namely HIV infection. The prevalence rate of HIV in pregnancy in KwaZulu-Natal is an estimated 37.7%. Furthermore, in women of reproductive age, the incidence of HIV infection is high (18.8%). The shallow trophoblast invasion and the lack of physiological conversion of the spiral arteries into small bore low resistance conduits is the primary cause behind the pathogenesis of pre-eclampsia. HIV-positive patients on HAART are predisposed to pre-eclampsia development. Trophoblast cells are stimulated to invade the maternal decidua by interacting cytokines and growth factors in the local environment through signal transduction pathways. Aberrant cell signaling and signaling molecule function impedes trophoblast invasion necessary for a healthy pregnancy, leading to endothelial dysfunction. As a result, the expression of cell signaling analytes may potentially be a predictive biomarker for patients at risk to pre-eclamptic development. This study investigated expression of STAT-3 and MEK-1 in HIV-associated pre-eclampsia, as a diagnostic tool of abnormal placentation in pre-eclampsia. Method: Venous blood samples of 40 normotensive and 40 pre-eclamptic patients further stratified by HIV status were collected at a large regional hospital for buffy coat extraction, followed by analysis of cell signalling analytes by the Bio-Plex Multiplex immunoassay. Results: The downregulation of both STAT-3 and MEK-1 expression was observed in pre-eclamptic pregnancies irrespective of HIV status, respectively (p < 0.05; p = 0.1526). No significance for STAT-3 (p = 0.0859) was detected between HIV-positive and HIV-negative groups irrespective of pregnancy type, although a lowered trend was observed in the HIV-positive group. Contrary to expected outcomes, MEK-1 expression was significantly decreased (p = 0.0102) in the HIV-positive group, irrespective of pregnancy type. Conclusion: This study demonstrated the downregulation of STAT-3 and MEK-1 expression in pre-eclampsia, corroborating a defective trophoblast invasion. The decreased expression of STAT-3 in HIV-infection may be attributed to HAART and/or to the reduced expression of IL-6 that stimulates STAT-3 phosphorylation. It is also plausible to assume that the downregulation of MEK-1 arises from non-phosphorylation of HIV-regulatory proteins. Additional studies, are required to further investigate the role of signal transduction pathways and its effect on HAART in pre-eclampsia development.


Master of Medical Science in Optics and Imaging. University of KwaZulu-Natal, Durban 2017.