Maternal and foetal angiogenic imbalance in congenital heart defects

Eur Heart J. 2014 Mar;35(11):701-7. doi: 10.1093/eurheartj/eht389. Epub 2013 Oct 24.


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)-2α, 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.

Keywords: Congenital heart defects; Placental growth factor; Soluble endoglin; Vascular endothelial growth factor; sFlt-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism*
  • Case-Control Studies
  • Endoglin
  • Female
  • Fetal Blood / chemistry
  • Fetus / metabolism
  • Heart Defects, Congenital / embryology*
  • Humans
  • Neovascularization, Physiologic / physiology
  • Placenta Growth Factor
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / metabolism
  • Pregnancy Proteins / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*


  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • PGF protein, human
  • Pregnancy Proteins
  • Receptors, Cell Surface
  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1