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Role of β-catenin in hypoxia-induced right ventricular hypertrophy



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Role of β-catenin in hypoxia-induced right ventricular hypertrophy


ZHOU Yang LIU Lingxi TANG Shihai PENG Huali

Department of Cardiothoracic Surgery, People’s Hospital of Leshan, Leshan, Sichuan Province, 614000; Department of Cardiovascular Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China


&beta-catenin cyanotic congenital heart disease myocardial hypertrophy hypoxia


Objective     To determine the role of β-catenin in hypoxia-induced right ventricular hypertrophy, and investigate the potential medical target. Methods     Myocardial tissue specimens were collected from the right ventricular outflow tract of 21 children with congenital heart disease during operation, who were hospitalized in the Department of Cardiovascular Surgery of Xinqiao Hospital from October 2015 to August 2016 (including 11 cases of cyanotic type, with postoperative diagnosis as Tetralogy of Fallot, and  blood oxygen saturation of ≤85%, and 10 cases of acyanotic type, with postoperative diagnosis as interventricular septal defect and right ventricular outflow tract stenosis, and blood oxygen saturation of ≥95%). The area of cardiomyocytes was measured by immunofluorescence assay, and the protein level of βcatenin in the cytoplasm and nucleus were determined by Western blotting. Twentyfive C57BL/6J mice were randomly divided into 4-week normoxia group, 4-week hypoxia group, and 4-week hypoxia+activator (CHIR-9901), +inhibitor (IWR-1) and +normal saline groups (n=5). After 4 weeks of hypoxia (10% O2) or normoxia, the rats were executed and the hearts were immediately taken out to isolate the right ventricle. The area of cardiomyocyte was detected by immunofluorescence assay. Western blotting was adopted to detect the protein level of βcatenin and Cyclin D1 in the cytoplasm and nucleus. In the 4-week hypoxia+activator, +inhibitor and +normal saline groups, the related agents were intraperitoneally injected in the hypoxic chamber at the beginning of the 4th week of hypoxia. After the heart was taken after the hypoxia, the weight of right ventricle and the area of cardiomyocytes were used to evaluate the degree of myocardial hypertrophy, and the cardiac function was measured by cardiac catheterization. Results     The cyanotic group had significantly larger area of cardiomyocytes (P<0.05), and lower protein level of β-catenin in the cytoplasm and nucleus as compared with the acyanosis group. The mouse model of chronic hypoxia showed larger area of cardiomyocytes (P<0.05), higher ratio of right ventricle weight to body weight  (P<0.05), lower right ventricular ejection fraction (P<0.05), and decreased expression level of β-catenin in the cytoplasm and nucleus.  Compared with the 4-week hypoxia+normal saline group, the 4-week hypoxia+activator group displayed smaller area of cardiomyocytes (P<0.05), lower ratio of right ventricle to body weight (P<0.05), increased right ventricular ejection fraction (P<0.05), and increased level of βcatenin in the nucleus and its downstream Cyclin D1. However, no such changes were observed in the 4-week hypoxia+inhibitor group (P>0.05). Conclusion     During the process of chronic hypoxiainduced right ventricular hypertrophy, β-catenin enters the nuclei after activation, and then alleviates myocardial hypertrophy and improves cardiac function.


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Last Update: 2017-08-23