Association of angiogenic factors (placental growth factor and soluble FMS-like tyrosine kinase-1) in preeclamptic women of African ancestry comorbid with HIV infection.

BACKGROUND: Preeclampsia is a significant cause of maternal and fetal morbidity and mortality, particularly in low- and middle-income countries like South Africa. AIM: The aim of our study was to investigate the association between placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1) in South African preeclamptic women of African ancestry, comorbid with HIV infection. METHODS: The study population consisted of women attending a regional hospital in Durban, South Africa, stratified by pregnancy type (normotensive pregnant and preeclampsia) and HIV status. Preeclampsia was defined as new-onset hypertension and proteinuria. DNA was obtained from whole blood. The SNPs of interest were rs722503 in sFlt-1 and rs4903273 in PlGF. RESULTS: Our findings suggest that single nucleotide polymorphisms of rs722503 analysis show no significant associations between the genotypic frequencies of rs722503 variants and preeclampsia risk in either HIV-negative or HIV-positive groups of women of African ancestry. Similarly, the rs493273 polymorphism showed no significant association with preeclampsia risk in either HIV-negative or HIV-positive pregnant women. Additionally, comparisons of dominant, recessive, and over-dominant allele models did not reveal significant associations. These findings suggest that these genetic variants may not significantly contribute to preeclampsia development in this African ancestry population. However, significant differences were observed in the rs4903273 genotype frequencies between normotensive and preeclamptic women, regardless of HIV status, over dominant alleles AA + GG vs AG showed a significant difference [OR = 2.706; 95% Cl (1.199-5.979); adjusted p = 0.0234*], also in normotensive compared to EOPE (OR = 2.804; 95% Cl (1.151-6.89) p = 0.0326* and LOPE (OR = 2.601; 95% Cl (1.0310-6.539) p = 0.0492*), suggesting that they may be the potential role of this variant in preeclampsia susceptibility. CONCLUSION: The findings suggest that the rs722503 and rs493273 polymorphisms do not significantly contribute to preeclampsia susceptibility in HIV-negative or HIV-positive pregnant women. However, the rs4903273 genotype frequencies showed notable differences between normotensive and preeclamptic women, indicating a potential association with preeclampsia development in the African ancestry population irrespective of HIV status.

Circulatory and Placental Expression of Soluble Fms-like Tyrosine Kinase- 1 and Placental Growth Factor in HIV-infected Preeclampsia.

An imbalance between angiogenic and anti-angiogenic factors plays a fundamental role in the pathogenesis of preeclampsia (PE). Studies have shown a dysregulation of sFlt-1 and placental growth factor (PlGF) in PE. However, there are differing reports on the levels of these pro-/antiangiogenic factors in HIV-infected preeclamptic and normotensive pregnancies, possibly due to highly active antiretroviral therapy (HAART) and its immune reconstitution effect. The study aimed to investigate the effect of hypertension and ARVs on circulating and placental pro- and antiangiogenic factors in HIV-infected PE. The level of sFlt-1 expression is elevated in PE compared to normal pregnancies. PlGF was altered by placental dysfunction. Antiretroviral therapy does not impact the angiogenic shift in PE development. The angiogenic imbalance evident in the circulatory system by higher sFlt-1 compared to PlGF levels is replicated in the placenta by reduced expression of PlGF receptors in comparison to sFlt-1 receptors. However, there is a lack of data that explore the relationship between HAART and anti-angiogenic factors in the placenta and the circulation of PE comorbid with HIV infection.

Are concentrations of clusterin and beta-2-glycoprotein I dysregulated in HIV associated preeclampsia?

OBJECTIVE: To evaluate the levels of serum beta-2-glycoprotein I (ß2GP1) and clusterin in the duality of Pre-eclampsia and HIV. METHOD: Stored serum samples collected from 72 pregnant women were stratified according to the pregnancy type (pre-eclamptic and healthy normotensive groups) and HIV status (positive or negative). A Bio-Plex multiplex immunoassay was used to determine the concentrations of clusterin and ß2GP1. RESULTS: Clusterin concentrations differed significantly (p = 0.01) between the HIV positive (+) (mean = 123 800 ng/ml; 95 % CI: 105 400-142 200) vs. HIV negative (-) (mean = 92 190 ng /ml; 95 %CI: 75 840-108 500) groups and across all groups (p = 0.0006). Beta-2-glycoprotein I concentration differed significantly based on HIV status (p < 0.0001); HIV+ (mean = 393 649 ng/ml; 95 %CI: 30 300-467 000) vs HIV- (mean = 224 309 ng/ml; 95 %CI: 154 000-294 700) and across all groups (p < 0.0001). No significant difference was observed between normotensive and Pre-eclamptic groups for both clusterin and ß2GPI. CONCLUSION: Serum concentrations of clusterin and ß2GPI were significantly increased in HIV positive pregnancies. It is postulated that both clusterin and ß2GPI may have a role in HIV disease progression. These findings need to be confirmed in studies having larger sample sizes and detailed information on anti-retroviral therapy.