Maternal and foetal angiogenic imbalance in congenital heart defects
Maternal and foetal angiogenic imbalance in congenital heart defects
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DOI：
10.1093/eurheartj/eht389
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发表时间：
2014-03-01
影响因子：
39.3
通讯作者：
Cabero, Lluis
中科院分区：
文献类型：
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作者：
Llurba, Elisa;Sanchez, Olga;Cabero, Lluis
目的动物模型显示血管生成与心脏发育异常有关。我们的目的是确定先天性心脏病（CHD）与母体和胎儿血液中血管生成/抗血管生成失衡之间是否存在关系，并研究胎儿心脏中血管生成因子的表达。对65例冠心病患者和204例正常人可溶性fms样酪氨酸激酶-1（sFlt-1）和可溶性内皮糖蛋白（sEng）进行了比较。检测23例CHD胎儿和8例对照组心脏组织中血管生成因子的表达和缺氧标志物。与对照组相比，CHD组血浆PlGF水平显著降低（367 33 vs. 566 26 pg/mL; P 0.0001），sFlt-1显著升高（2726 450 vs. 1971 130 pg/mL，P 0.0438）。CHD胎儿的脐带血浆sFlt-1（442 76 vs. 274 26 pg/mL; P 0.0285）和sEng（6.76 0.42 vs. 4.99 0.49 ng/mL，P 0.0041）水平较高。与正常心脏相比，CHD胎儿心脏组织中血管内皮生长因子（VEGF）、sFlt-1、慢性缺氧标志物和抗氧化活性的表达显著升高（VEGF、sFlt-1、HIF-2、HO-1、sFlt-1.92、HO-1.62、HIF-2.45）。结论先天性心脏病患者存在一种内在的血管生成障碍，这种障碍似乎存在于母体和胎儿的循环和胎儿心脏中。我们的数据表明，血管生成-抗血管生成因子的失衡与人类心脏的发育缺陷有关。
Aims 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.Methods and Results 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)-2, 1.45-fold; HO-1, 1.62-fold; SOD1, 1.31-fold).Conclusion 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.