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

Yang ZHOU; Lingxi LIU; Shihai TANG; Huali PENG

doi:10.16016/j.1000-5404.201612179

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

更新时间：2026-01-09

- Role of β-catenin in hypoxia-induced right ventricular hypertrophy
- Journal of Third Military Medical University Vol. 39, Issue 16, Pages: 1637-1642(2017)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201612179
  CLC：
- Received：29 December 2016，
  
  Published：30 August 2017
- 稿件说明：
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Yang ZHOU, Lingxi LIU, Shihai TANG, et al. Role of β-catenin in hypoxia-induced right ventricular hypertrophy[J]. Journal of Third Military Medical University, 2017, 39(16): 1637-1642.
DOI：

Yang ZHOU, Lingxi LIU, Shihai TANG, et al. Role of β-catenin in hypoxia-induced right ventricular hypertrophy[J]. Journal of Third Military Medical University, 2017, 39(16): 1637-1642. DOI： 10.16016/j.1000-5404.201612179.

摘要

Abstract

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

d 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 (

=5). After 4 weeks of hypoxia (10% O

) 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 (

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 (

0.05)

higher ratio of right ventricle weight to body weight (

0.05)

lower right ventricular ejection fraction (

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 (

0.05)

lower ratio of right ventricle to body weight (

0.05)

increased right ventricular ejection fraction (

0.05)

and increased level of β-catenin in the nucleus and its downstream Cyclin D1. Howev

no such changes were observed in the 4-week hypoxia+inhibitor group (

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.

关键词

Keywords

references

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