Abstract

BackgroundPatients with transposition of the great arteries are likely to survive surgery despite severe pulmonary artery hypertension. However, the underlying mechanisms remain largely unknown. The present study aimed to test the hypothesis that high blood oxygen saturation may protect the pulmonary artery from remodeling.MethodsAn in vitro pulmonary artery perfusion model was successfully performed by connecting rabbit pulmonary artery to a closed perfusion circuit. Twenty-five rabbits were divided randomly into 5 groups according to exposure conditions: Normal Control (NC) group (unperfused normal pulmonary artery), High Saturation (HS) group (oxygen saturation range: 90–100%), Medium Saturation (MS) group (oxygen saturation: 65–75%); Low Saturation (LS) group (oxygen saturation: 40–50%), and anti-hypoxia inducible factor-1α (anti-HIF-1α) group (oxygen saturation range: 40–50%, and LW6, which is a novel HIF-1α inhibitor; was added). By staining and optical microscopy examination, pathological morphology was analyzed, and the protein expression levels of HIF-1α, angiotensin-II (Ang-II), endothelin-1 (ET-1), Rho-associated protein kinase-1 (Rock-1), and matrix metallopeptidase-2 (MMP-2) were determined by Western blotting.ResultsThe amounts of elastin, muscle, and collagen and the protein levels of ET-1, HIF-1α, Rock-1, and MMP-2, increased significantly with decreased oxygen saturation in the perfusion circuit. A significant improvement in pathological morphology was observed in the anti-HIF1α group. The expression of HIF-1α, ET-1, Ang-II, Rock-1, and MMP-2 in the anti-HIF1α group was also significantly lower than that in the LS group.ConclusionsIn the closed perfusion model, high blood oxygen saturation alleviated pulmonary vascular structural remodeling. Similar beneficial effects were observed when inhibiting the HIF-1α protein, suggesting a key role for HIF-1α in pulmonary artery remodeling.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call