Mechanisms of pulmonary hypertension related to ventricular septal defect in congenital heart disease.
BACKGROUND
The aim of this study was to investigate differences in molecular mechanisms of pulmonary hypertension between patients with complete transposition of the great arteries (TGA) combined with ventricular septal defect (VSD) and those with VSD alone.


METHODS
Twenty-four consecutive patients with pulmonary hypertension (mean pulmonary artery pressure > 30 mm Hg) underwent surgical correction of TGA + VSD (n = 10) or VSD alone (n = 14). Lung specimens were taken from the right middle lobe before cardiopulmonary bypass (CPB). Extent of pulmonary hypertension was graded according to the Heath-Edwards pathologic classification. Enzyme-linked immunosorbent assay (ELISA) was used to determine expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), endothelin-1 (ET-1), endothelin A and B receptors (ET-AR, ET-BR), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), and tissue inhibitor of metalloproteinase (TIMP).


RESULTS
There were no statistically significant differences in age, height, weight, VSD diameter, or preoperative pulmonary artery pressure between groups. Hemoglobin level, pulmonary artery oxygen saturation, and reduction in postoperative pulmonary artery pressure were significantly higher in patients undergoing correction of TGA + VSD (p < 0.05). All patients had grade 0 to II Heath-Edwards morphologic changes in lung biopsy samples. Expression of eNOS and MMP-2 was significantly lower in the TGA + VSD group than in the VSD-alone group (eNOS, 280.13 ± 101.92 ng/mg versus 488.41 ± 249.60 ng/mg; p < 0.05; MMP-2, 31.68 ± 15.36 ng/mg versus 69.28 ± 49.12 ng/mg; p < 0.05). There were no statistically significant differences between groups in expression of iNOS, ET-1, ET-AR, ET-BR, MMP-9, or TIMP.


CONCLUSIONS
In patients with TGA + VSD, high oxygenation in the pulmonary circulation decreases expression of MMP-2 and eNOS, which may affect the progress and reversibility of pulmonary hypertension.
State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, The People's Republic of China. xiangbin428@hotmail.com
Xiangbin
X
Pan
Zhe
Z
Zheng
Shengshou
S
Hu
Shoujun
S
Li
Yingjie
Y
Wei
Yajuan
Y
Zhang
Xiansheng
X
Cheng
Kai
K
Ma
D002675:Child, Preschool; D006345:Heart Septal Defects, Ventricular / Q000150:complications*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology*; D007223:Infant; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D014188:Transposition of Great Vessels / Q000150:complications*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
C066737:RHOA protein, human; D052250:Nitric Oxide Synthase Type III; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020742:rhoA GTP-Binding Protein