Maternal and foetal angiogenic imbalance in congenital heart defects

作者：Llurba Elisa^*; Sanchez Olga; Ferrer Queralt; Nicolaides Kypros H; Ruiz Aina; Dominguez Camen; Sanchez de Toledo Joan; Garcia Garcia Belen; Soro Gemma; Arevalo Silvia; Goya Maria; Suy Anna; Perez Hoyos Santiago; Alijotas Reig Jaume; Carreras Elena; Cabero Lluis

来源：European Heart Journal, 2014, 35(11): 701-+.

DOI：10.1093/eurheartj/eht389

• Congenital heart defects
• Placental growth factor
• sFlt-1
• Vascular endothelial growth factor
• Soluble endoglin

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.

• 出版日期2014-3