医学
胎盘生长因子
血管生成
内科学
缺氧(环境)
血管内皮生长因子
内分泌学
脐带血
血管生成素受体
胎儿
可溶性fms样酪氨酸激酶-1
血管内皮生长因子A
怀孕
血管内皮生长因子受体
生物
有机化学
化学
氧气
遗传学
作者
Elisa Llurba,Olga Sánchez,Queralt Ferrer,Kypros H. Nicolaides,Alba Ruiz,Camen Domínguez,Joan Sánchez-de-Toledo,Belén García-García,G. Soro,Sílvia Arévalo,María Goya,Anna Suy,Santiago Pérez-Hoyos,Jaume Alijotas‐Reig,Elena Carreras,L. Cabero
标识
DOI:10.1093/eurheartj/eht389
摘要
Animal models showed that angiogenesis is related to abnormal heart development. Our objectives were to ascertain whether a relationship exists between congenital heart defects (CHDs) and angiogenic/anti-angiogenic imbalance in maternal and foetal blood and study the expression of angiogenic factors in the foetal heart. Maternal and cord blood placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were compared in 65 cases of CHD and 204 normal controls. Angiogenic factor expression and markers of hypoxia were measured in heart tissue from 23 CHD foetuses and 8 controls. In the CHD group, compared with controls, plasma PlGF levels were significantly lower (367 ± 33 vs. 566 ± 26 pg/mL; P < 0.0001) and sFlt-1 significantly higher (2726 ± 450 vs. 1971 ± 130 pg/mL, P = 0.0438). Foetuses with CHD had higher cord plasma sFlt-1 (442 ± 76 vs. 274 ± 26 pg/mL; P = 0.0285) and sEng (6.76 ± 0.42 vs. 4.99 ± 0.49 ng/mL, P = 0.0041) levels. Expression of vascular endothelial growth factor (VEGF), sFlt-1, markers of chronic hypoxia, and antioxidant activity were significantly higher in heart tissue from CHD foetuses compared with normal hearts (VEGF, 1.59-fold; sFlt-1, 1.92-fold; hypoxia inducible factor (HIF)-2α, 1.45-fold; HO-1, 1.62-fold; SOD1, 1.31-fold). An intrinsically angiogenic impairment exists in CHD that appears to be present in both the maternal and foetal circulation and foetal heart. Our data suggest that an imbalance of angiogenic-antiangiogenic factors is associated with developmental defects of the human heart.
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