• Guangqing Cao, Chuanzhen Liu, Zhaojie Wan, Kai Liu, Hourong Sun, Xiangfei Sun, Mengmeng Tang, Weidong Bing, Shuming Wu, Xinyan Pang, and Xiquan Zhang.
• The Key Laboratory of Cardiovascular Remodeling and Function Research, Division of Medicine, Department of Cardiovascular Surgery, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
• J. Thorac. Cardiovasc. Surg. 2015 Sep 1;150(3):621-32.

BackgroundHyperkinetic pulmonary arterial hypertension (PAH) is a common complication in congenital heart disease, and affects operations, indications, and prognoses for patients. Gene-based stem cell transplantation is an alternative treatment that can attenuate PAH.MethodsHyperkinetic PAH rabbit models were successfully established, using common carotid artery and jugular vein anastomosis. Endothelial progenitor cells (EPCs) were isolated from the bone marrow, cultured, and transfected with human hypoxia inducible factor-1 alpha (hHIF-1α), using lentiviruses. Two weeks after the transfected EPCs were transplanted into the rabbits, catheterization was applied to collect hemodynamic data. The hypertrophy of the right ventricle and pulmonary vascular remodeling were evaluated by measuring the right ventricle hypertrophy index, the medial wall thickness, and the medial wall area. Western blot and immunohistochemistry analyses were used to detect the expression of hHIF-1α in the pulmonary small arteries.ResultsTwo weeks after transplantation, systolic pulmonary arterial pressure and mean pulmonary arterial pressure were both attenuated. The hypertrophy of the right ventricle, and pulmonary vascular remodeling were reversed. Expression of hHIF-1α in the hHIF-1α-transfected EPCs that had been transplanted was high, and the number of pulmonary small arteries had increased. In addition, combined HIF-1α and homogeneous EPC therapy was more effective at attenuating PAH and increasing the density of pulmonary small arteries, compared with EPC transplantation alone.ConclusionsBoth the therapy with HIF-1α-transfected EPCs, and EPC transplantation, attenuated shunt flow-induced PAH, by means of an angiogenic effect. The former therapeutic method was more effective.Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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