Lung remodeling in a porcine model of cyanotic congenital heart defect with decreased pulmonary blood flow.
BACKGROUND
Hypoperfusion of the pulmonary vascular bed under the condition of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the mechanistic understanding of this disease, we examined the biochemical and morphological changes of the lung in a relevant animal model and provided valuable insights into the underlying mechanisms of the pathogenesis of pulmonary hypotension.


METHODS
A model of congenital heart defect with decreased pulmonary blood flow was implemented into 8 piglets (the cyanosis group). Another 8 piglets underwent a sham operation (the control group). Two months postoperatively, lung biopsy specimens were harvested for the measurement of the expression levels of MMP-2, MMP-9, TIMP-1, VEGF, and type I and type III collagens. Moreover, the light-microscopic morphology, morphometry, and ultrastructure of lobes were examined.


RESULTS
Compared to the controls, the histopathological changes of the pulmonary vasculature in the cyanosis group showed evident hypoplasia and degeneration. The expression levels of MMP-2, MMP-9, TIMP-1, VEGF, and type I collagen, as well as the microvessel density, in the cyanosis group were significantly lower than those in the control group, whereas the level of type III collagen in the cyanosis group was significantly higher than that in the control group.


CONCLUSIONS
The observed morphological changes may represent an adaptive reaction to the prolonged decrease of pulmonary blood flow. The underlying mechanism of lung remodeling may be attributed to the changes in the expression of structural proteins and cytokines in the pulmonary extracellular matrix induced by modulating factors.
Pediatric Cardiac Center, Beijing Anzhen Hospital, The Capital Medical University,   Beijing,   China.
Yaoqiang
Y
Xu
Yinglong
Y
Liu
Zhiqiang
Z
Li
Junwu
J
Su
Gang
G
Li
Lizhong
L
Sun
D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D024042:Collagen Type I / Q000032:analysis; D024061:Collagen Type III / Q000032:analysis; D003490:Cyanosis / Q000503:physiopathology*; D004195:Disease Models, Animal; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D055806:Microvessels / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000502:physiology*; D013552:Swine; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D024042:Collagen Type I; D024061:Collagen Type III; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9