Placenta Growth Factor and Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia and Normotensive Pregnant Nigerian Women

Background: Preeclampsia (PE) is still one of the leading causes of maternal/perinatal morbidity/mortality in Nigeria. Imbalance between placenta growth factor (PLGF) and soluble fms-like tyrosine kinase 1 (sFlt1) has been reportedly present both before and after the manifestation of PE;however, Nigerian data regarding these angiogenesis-related substances are lacking. We here attempted to determine the maternal serum level of PLGF and sFlt1 and sFlt1/PLGF ratio in PE vs. non-PE women in Lagos State University Teaching Hospital, Nigeria. Methods: An observational cross-sectional study was made on 75 women with PE and 75 age-gestational-age matched women without PE, as case and control, respectively. Levels of sFlt-1, PIGF and the sFlt-1: PIGF ratio was compared between the two. Results: Serum levels of Flt-1 and sFlt1/PIGF ratio were significantly higher in PE patients (6581.86 ± 865.75, and 146.42 ± 92.43) than in the normotensive control (4584.52 ± 1479.6 and 11.60 ± 6.42). PIGF was significantly lower in PE patients (70.14 ± 51.03) than the normotensives (494.06 ± 475.8). There were positive and negative correlations between the sFlt-1 and PLGF respectively and mean arterial blood pressure. Conclusion: Serum sFlt-1, sFlt1/PIGF ratio was significantly higher and PIGF levels were significantly lower in PE than normotensive control in Nigerian population.

Effect of Bushen Yiqi Huoxue Recipe on Placental Vasculature in Pregnant Rats with Fetal Growth Restriction Induced by Passive Smoking

Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.

Targeted Antagonism of Vascular Endothelial Growth Factor Reduces Mortality of Mice with Acute Respiratory Distress Syndrome

Summary:Acute respiratory distress syndrome(ARDS)is associated with a mortality of 45%.Our previous rescarch indicated that anti-vascular endothelial growth factor(VEGF)could maintain the normal structure and function of the respiratory barrier.However,systemic application of VEGF antagonists would lead to animal death.This study attempts to study the targeted drug delivery for ARDS.In this study,we used soluble fims-like tyrosine kinase-1(sFlt)-targeted ultrasound microbubbles to antagonize the effect of VEGF on lung tissue.Ninety male BALB/C mice were randomly assigned to 6 groups:phosphate buffer saline(PBS)group(PBS+PBS);blank group(PBS+empty microbubbles);lipopolysaccharide(LPS)group(LPS+PBS);ARDS group(LPS tempty microbubbles);control group(PBS+sFlt microbubbles);and treatment group(LPS+sFIt microbubbles).After administration of LPS or PBS in the corresponding groups,the sFlt-targeted microbubbles or empty microbubbles were injected into the blood circulation.Then the lungs were irradiated with ultrasound,which ruptured the drug-loaded microbubbles and helped release drugs to the lung tissues targeted.The lung injury score,lung wet/dry ratio(W/D),liver and kidney functions,and the mortality of the mice in all groups were investigated at the predetermined time point.The difference in mortality between groups was examined by Fisher test.Other data were analyzed by onc-way analysis of variance(ANOVA).A value of P<0.05 indicates that the difference was significant.The results showed that the PaO2 levels were normal in the PBS group,the blank group,and the control group.The LPS group and ARDS group showed significant hypoxia.PaO2 was improved significantly in the treatment group.The lung injury score and W/D were normal in the PBS group,the blank group,and the control group.The lung injury score and W/D increased significantly in the LPS group and ARDS group and decreased in the treatment group(P<0.05).The mortality rate of the ARDS model was 60%(95%confidence interval 47.5%-72.5%),and that with sFlt-targeted microbubbles was significantly lower at only 40%(95%confidence interval 27.5%-52.5%,P<0.05).It was concluded that anti-VEGF with sFIt targeted ultrasound microbubbles attenuated the lung injury and ultimately reduced the 7-day mortality effectively.It might be a suitable therapeutic tool for the treatment of ARDS.

Maternal Vascular Dysfunction in Congenital Heart Defects

Background:Research on fetal congenital heart defect(CHD)mostly focuses on etiology and mechanisms.However,studies on maternal complications or pathophysiology are limited.Our objective was to determine whether vascular dysfunction exists in pregnant women carrying a fetus with congenital heart defects.Methods:We conducted a case-control study.27 cases of pregnant women carrying a fetus with major CHD admitted to our hospital for delivery between April 2021 and August 2022 were selected.Every case was matched with about 2 pregnant complication-free controls without fetal abnormalities.The proangiogenic and anti-angiogenic factors and pregnancy outcomes were compared.Results:The proangiogenic factors include vascular endothelial growth factor(VEGF)and placental growth factor(PlGF).The anti-angiogenic factors involve soluble fms-like tyrosine kinase 1(sFlt-1)and soluble endoglin(sEng).No differences were found in maternal plasma concentrations of PlGF,VEGF,and sFlt-1 between case-control groups when analyzed at 36 weeks≤gestational age(GA)<39 weeks and 39 weeks≤GA≤41 weeks.The concentrations of sEng in maternal plasma in the fetal CHD group were significantly higher than those in the control group:0.60(0.77)vs.0.32(0.26)ng/ml at 36 weeks≤GA<39 weeks,p=0.001 and 0.75(0.55)vs.0.28(0.27)ng/ml at 39 weeks≤GA≤41 weeks,p<0.001.Conclusion:Vascular dysfunction exists in pregnant women with fetal congenital heart defects,manifesting significantly elevated sEng concentration at delivery.