Abstract
Preeclampsia (PE) is a major cause of maternal and new-born morbidity and mortality. Angiogenic factors contribute a major role in the vascular dysfunction associated with PE. We investigated the circulating levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and soluble Feline McDonough Sarcoma (fms)-like tyrosine kinase-1 (sFlt1), their association with PE and diagnostic performance of disease among pregnant women in Uganda. Using a case-control study design, 106 women with PE and 106 with normal pregnancy were enrolled. Demographic and clinical characteristics, and anticoagulated blood samples were collected from participants. Plasma VEGF, PlGF and sFlt1 levels were measured using Luminex and enzyme linked immunosorbent assays (ELISA). Conditional logistic regression was used to explore association of angiogenic factors with PE and receiver operating characteristic analysis was performed to investigate PE diagnostic performance. Levels of VEGF and PIGF were significantly lower in cases compared to controls (VEGF: median = 0.71 pg/ml (IQR = 0.38-1.11) Vs 1.20 pg/ml (0.64-1.91), p-value<0.001 and PlGF: 2.20 pg/ml (1.08-5.86) Vs 84.62 pg/ml (34.00-154.45), p-value<0.001). Plasma levels of sFlt1 were significantly higher in cases than controls (median = 141.13 (71.76-227.10) x103 pg/ml Vs 19.86 (14.20-29.37) x103 pg/ml). Increasing sFlt1 levels were associated with increased likelihood of PE (aOR = 4.73; 95% CI, 1.18-19.01; p-value = 0.0287). The sFlt1/PlGF ratio and sFlt1 had a better performance for diagnosis of PE, with AUC = 0.95 (95% CI, 0.93-0.98) followed by PlGF with AUC = 0.94 (95% CI, 0.91-0.97). Therefore, sFlt1, sFlt1/PlGF ratio and PlGF are potential candidates for incorporation into algorithms for PE diagnosis in the Ugandan population.
Highlights
Preeclampsia (PE) is a pregnancy complication that affects 3–8% pregnant women worldwide, with a higher burden among African women [1, 2]
The systemic vascular dysfunction is associated with impaired angiogenesis, vascular permeability and endothelial cell function, which culminate into high blood pressure, exaggerated systemic inflammatory response and end organ damage [6, 7]
Binding by Sarcoma (fms)—like tyrosine kinase-1 (sFlt1) prevents Vascular endothelial growth factor (VEGF) and Placental growth factor (PlGF) signalling via the VEGF-1 receptor on endothelial cells, thereby disrupting endothelial cell activation, leading to abnormal function and vascular dysfunction [10, 11]
Summary
Preeclampsia (PE) is a pregnancy complication that affects 3–8% pregnant women worldwide, with a higher burden among African women [1, 2]. The systemic vascular dysfunction is associated with impaired angiogenesis, vascular permeability and endothelial cell function, which culminate into high blood pressure, exaggerated systemic inflammatory response and end organ damage (such as the kidney and liver) [6, 7]. The preeclamptic placenta releases excess amounts of antiangiogenic soluble Feline McDonough Sarcoma (fms)- like tyrosine kinase-1 (sFlt-1) into maternal circulation, which binds free circulating proangiogenic Vascular endothelial growth factor (VEGF) and Placental growth factor (PlGF), leading to an antiangiogenic state [8, 9]. Binding by sFlt prevents VEGF and PlGF signalling via the VEGF-1 receptor on endothelial cells, thereby disrupting endothelial cell activation, leading to abnormal function and vascular dysfunction [10, 11]
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