• Haoran Miao, Fan Qiu, Lidong Zhu, Bo Jiang, Yanliang Yuan, Bing Huang, and Yiqian Zhang.
• Department of Thoracic Cardiovascular Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China; Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
• J. Thorac. Cardiovasc. Surg. 2021 Jun 1; 161 (6): e417-e434.

ObjectiveTo select a suitable combination of classic angiogenic and vascular stabilization factors to improve the proliferation and maturity of neovascularization of lung tissue in a rat pulmonary arterial hypertension (PAH) model.MethodsPAH rat model was established by intraperitoneal injection of monocrotaline. Proangiogenic factors hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), as well as vascular stabilization factors angiopoietin-1 (Ang-1), platelet-derived growth factor, and transforming growth factor-beta were transfected by pairs into the lung tissue of rats with PAH through lentivirus. Four weeks later, pulmonary artery angiography and hemodynamic parameters were determined to testify the remission of PAH. Immunofluorescence staining and Western blot were performed to investigate the structure and function of neovascularization.ResultsThe pulmonary artery pressure and weight index of the right ventricle in HGF+Ang-1 and VEGF+Ang-1 groups were significantly decreased compared with vehicle group. The contrast medium filling time and right pulmonary artery root diameter were also significantly decreased. In addition, the maturity and perfusion of neovascularization in HGF+Ang-1 and VEGF+Ang-1 groups were promoted compared to vehicle group, and vascular leakage was reduced. Finally, the adherens junction integrity of vascular endothelial cells in HGF+Ang-1 and VEGF+Ang-1 combinations was upregulated compared with other combinations.ConclusionsHGF+Ang-1 transfection and VEGF+Ang-1 transfection alleviate PAH by promoting maturation and stability of new blood vessels, which may be potential candidates for PAH treatment.Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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