Hepatocyte growth factor and epidermal growth factor in HIV associated preeclampsia.

Abstract

Background: The survival or death of a cell is reliant upon growth factors. Hepatocyte and Epidermal Growth Factor (HGF and EGF) promote vital cellular processes such as cell survival, proliferation, differentiation, growth, invasion and repair via various pathways. Hence these growth factors facilitate normal pregnancy. In complications such as preeclampsia (PE), decreased trophoblast invasion results in defective spiral artery remodeling, which leads to decreased blood flow and a hypoxic micro-environment. In South Africa (SA), HIV infection and PE are the leading causes of maternal mortality and morbidity. In light of the high prevalence of HIV infection and PE in SA, this study aimed to determine the concentrations of HGF and EGF in HIV associated PE. Methods: Post ethics approval, serum samples were collected from normotensive HIV-negative (n = 20); normotensive HIV-positive (n = 20); preeclamptic HIV-negative (n = 20) and preeclamptic HIV-positive (n = 20) women. All HIV-positive women received Highly Active Anti-Retroviral Treatment (HAART). Quantification and analysis of HGF and EGF expression was attained by using the Bio-Plex multiplex immunoassay technique. Results: As expected there was a statistically significant difference between gestational age, systolic and diastolic blood pressures across the study groups (p<0.0001). No significant difference was noted in maternal age (p=0.16), parity (p=0.47) and maternal weight (p=0.36) across all study groups. Irrespective of pregnancy type, HGF was significantly increased in HIV-positive women vs HIV-negative women (p=0.0225). However, no statistical significance was found based on pregnancy type (p=0.8890). A significant decrease of HGF expression was noted between normotensive HIV-negative and normotensive HIV-positive women (p=0.0022). Irrespective of pregnancy type, EGF was found to be significantly elevated in HIV-positive compared to HIV-negative women (p=0.0055). In addition, preeclamptic women displayed a higher EGF level compared to normotensive women (p=0.003), regardless of HIV status. The Epidermal Growth Factor was significantly down-regulated in normotensive HIV-negative group vs normotensive HIV-positive (p<0.001), preeclamptic HIV-positive (p<0.001) and preeclamptic HIV-negative groups (p<0.001). Conclusion This novel study displays a significant up-regulation in the expression of HGF and EGF in HIV infection during pregnancy, reflecting an immune reconstitution following HAART. These findings may be caused due to the HIV accessory protein Tat that inhibits growth factor function thereby, negatively impacting cell migration. The up-regulation of EGF expression in PE, may be responsible for impaired trophoblast cell invasion. As anticipated in HIV associated PE, EGF expression increased in HIV infected pregnancies and PE. The expression Epidermal Growth Factor in HIV associated PE, may be used as a risk indicator, predicting PE development prior to the manifestations of clinical signs and symptoms.