Role of nitric oxide, angiogenic growth factors and biochemical analysis in preeclampsia.

Preeclampsia, a pregnancy-related hypertensive disorder, is one of the leading causes of fetal and maternal mortality and morbidity globally. Angiogenic growth factors, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are involved in the generation of new blood vessels required for placental development and physiological functions, while nitric oxide (NO) acts as vasodilator and also plays a role in angiogenesis. The objective of this study was to evaluate the role of NO, angiogenic growth factors (VEGF and PIGF) and other biochemical parameters in the development of preeclampsia among pregnant mothers. A complete clinical history, including anthropometric measurements and biochemical investigations, including renal function tests, liver function tests and lipid profile were performed among twenty preeclampsia patients aged 19 to 32 yrs. Results were compared with age-matched normotensive pregnant mothers. The body weight, body mass index (BMI), blood pressure, concentrations of urea, uric acid and triglyceride and activities of transaminase enzymes (aspartate transaminase, AST and alanine transaminase, ALT) in serum were significantly higher (p<0.05) than normotensive subjects. Serum concentrations of VEGF, PlGF and NO were significantly decreased (p<0.005) in preeclamptic patients. NO was found negatively correlated with body weight (r = -0.369, p<0.05), systolic blood pressure (r = -0.822, p<0.005), diastolic blood pressure (r = -0.714, p<0.005) and was positively correlated with VEGF (r = 0.464, p<0.005) and PlGF (r = 0.546, p<0.005). VEGF and PlGF showed significant (p<0.005) negative correlation with systolic and diastolic blood pressure and PlGF was significantly correlated with triglyceride (r = -0.379). However, no significant correlation was observed between the VEGF and PlGF. In conclusion, the results indicated that body weight, triglyceride, angiogenic growth factors and NO might associate with preeclampsia development.

Prediction of pre-eclampsia during early pregnancy in primiparas with soluble fms-like tyrosine kinase-1 and placental growth factor.

Background. We hypothesized that pre-eclampsia (PE) can be predicted early in primiparas by measuring serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Methods. All normotensive primiparas attending the antenatal clinics of Aga Khan University Hospital and Aga Khan Hospital for Women, Karachi, Pakistan without any known risk factor for PE were invited to participate in the study. They were divided into two groups based on the development of PE. Their blood samples were collected at 8–15, 16–22, 23–28, 29– 34 weeks of pregnancy and once within 1 week of delivery. All samples were analysed for sFlt-1 and PlGF. Results. Six hundred and eleven (46.7%) of 1307 recruited primiparas completed the study according to the protocol. Of these, 39 (6.4%) women developed PE. The difference in serum sFlt-1 was evident as early as 15 weeks of gestation. Higher levels of serum sFlt-1 were present in women who later developed PE. Relatively higher levels of PlGF were observed in non-PE women compared to PE women up to 22 weeks of gestation. However, after 23 weeks of pregnancy, PlGF levels increased in both the groups, but less so in the PE group. Receiver operator characteristics (ROC) curve analysis showed that even in early pregnancy (<15 weeks of gestation), serum sFlt-1 alone has the potential to predict PE with area under the curve (AUC), sensitivity and specificity of 0.81, 75.9 and 72.4, respectively. Conclusion. PE can be predicted in primiparas in the early part of second trimester with serum levels of sFlt-1 and in the later part of second trimester with serum levels of PlGF.

Circulating angiogenic factors in pregnancies complicated by pre-eclampsia.

Background. Pre-eclampsia is an inflammatory disorder characterized by diffuse endothelial dysfunction possibly secondary to impaired trophoblast invasion of the spiral arteries during implantation. It is associated with alterations in maternal serum concentrations of vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). We did a case–control study to ascertain whether pre-eclampsia is associated with changes in serum concentrations of VEGF, PlGF and sFlt-1 in Indian patients. Methods. Serum samples were obtained from 40 women with pre-eclampsia and 40 normotensive, non-proteinuric pregnant women. The levels of VEGF, PlGF and sFlt-1 were analysed using ELISA. Results. In the sera of pregnant women with pre-eclampsia, the levels of sFlt-1 were significantly higher than those in the sera of normotensive, non-proteinuric pregnant women (median 11 295.25 v. 2936.2 pg/ml, p<0.0001), whereas there was a significant reduction in the levels of free VEGF (mean [SD] 170.53 [36.56] pg/ml v. 254.61 [47.39] pg/ml, p<0.0001) and PlGF (mean [SD] 236.77 [93.70] pg/ml v. 744.98 [168.55] pg/ml, p<0.0001). Conclusion. An increase in sFlt-1 levels and a simultaneous decrease in free VEGF and PlGF levels in the sera of women with pre-eclampsia as compared with normotensive, nonproteinuric pregnant women suggest that an imbalance between the levels of these pro- and anti-angiogenic factors may have a role to play in the pathogenesis of pre-eclampsia.

Relevância clínica dos fatores de angiogênese na pré-eclâmpsia / Clinical relevance of angiogênese factor in preeclampsia

O desenvolvimento de hipertensão durante a gravidez continua sendo uma causa significante de morte materna em todo o mundo e no Brasil é particularmente preocupante. Na gravidez, 6-8 porcento das mulheres desenvolvem pré-eclâmpsia, a qual tem sido considerada a principal causa de morbimortalidade materno-fetal. Embora de etiologia indefinida, novas evidências sugerem que fatores angiogênicos produzidos pela placenta desempenham papéis essenciais nesse processo. Estes fatores agem local e sistemicamente, promovendo alterações materno-fetais para atender à crescente demanda metabólica e à expansão de volume. A busca por fatores angiogênicos como possíveis mediadores da disfunção endotelial sistêmica generalizada tem sido convincente em mostrar que a expressão aumentada e níveis elevados do fator solúvel similar à tirosina-cinase-I (sFIt-I), alterações na produção/função do fator de crescimento do endotélio vascular (VEGF) e do fator de crescimento placentário (PIGF) são eventos determinantes dos fenótipos da pré-eclâmpsia (hipertensão e proteinúria). O mecanismo proposto é que o sFIt-I neutraliza os efeitos vasodilatador e angiogênico do VEGF/PIGF. O resultado do desequilíbrio na produção/função desses fatores leva à disfunção endotelial, com conseqüências hipertensivas. Esta revisão sumariza o entendimento atual do papel dos fatores angiogênicos na gravidez e sua relação com o endotélio materno. Também avalia as alterações dos marcadores de angiogênese e suas repercussões na patogênese, diagnóstico e predição da pré-eclâmpsia.

Maternal and fetal concentration of serum placental growth factor and their correlation to glycemic control and doppler study in diabetic and normal pregnancy

To determine whether maternal diabetes is associated with altered human placental growth factor [PIGF] level in serum of both mother and fetus and study he relation between PIGF and Doppler parameters, Prospective analytic comparative study. 30 normal pregnant female, 60 patients with gestational diabetes, 30 diabetic controlled and 30 diabetic uncontrolled. PIGF was measured in stored maternal serum samples taken in the 3[rd] trimester and cord sample of their babies after delivery by enzyme-linked immunosorbent assays [ELISA]. Diabetes during pregnancy was diagnosed with the 75-g oral glucose tolerance test and by applying world health organization criteria. Doppler velocimetry of umbilical vessels was evaluated for vascular impedance, in terms of pulsatility index and S/D ratio. Insignificant difference in serum maternal PIGF in both diabetic and non diabetic groups in the third trimester [p 0.139]. Cord serum PIGF was lower in diabetic controlled than uncontrolled group [p 0.023]. But there was significant negative correlation between maternal PIGF and cord serum PIGF in control [r -.537] and uncontrolled diabetic group [r -.384], p<0.05. Significant positive correlation between cord serum PIGF and S/D ratio was found [r .383], p<0.037. Significant negative correlation was found between PIGF in maternal serum and Doppler parameters in diabetic controlled group [r - 0.362], p value < 0.049 and in diabetic uncontrolled group [r = 0.500], p value < .005. FBS was positively correlated to cord serum PIGF in both controlled [r .603 and p value <0.001] and uncontrolled diabetic groups [r .934 and p value <0.001]. Maternal serum PIGF is similar in 3[rd] trimester in diabetic pregnancy and in control group. Serum cord PIGF was higher in uncontrolled than controlled diabetics. Significant negative correlation between maternal PIGF and cord serum PIGF in control and uncontrolled diabetic group. Rise in cord serum PIGF is related to chronic fetal hypoxia as evident by abnormal Doppler. Further studies are needed to confirm results