Cardiac-specific Haploinsufficiency of Beta-catenin Attenuates Cardiac Hypertrophy but Enhances Fetal Gene Expression in Response to Aortic Constriction

Overview

Journal J Mol Cell Cardiol

Specialty Cardiology & Vascular Diseases

Date 2007 Aug 4

PMID 17673255

Citations 32

Authors

Jiaxiang Qu

Jibin Zhou

Xian Ping Yi

Baojun Dong

Hanqiao Zheng

Lisa M Miller

Xuejun Wang

Michael D Schneider

Faqian Li

Affiliations

Soon will be listed here.

Abstract

In addition to its role in cell adhesion, beta-catenin is an important signaling molecule in the Wnt/Wingless signaling pathway. Recent studies have indicated that beta-catenin is stabilized by hypertrophic stimuli and may regulate cardiac hypertrophic responses. To explore the role and requirement of beta-catenin in cardiac development and hypertrophy, we deleted the beta-catenin gene specifically in cardiac myocytes by crossing loxP-floxed beta-catenin mice with transgenic mice expressing a Cre recombinase under the control of the alpha-myosin heavy chain promoter. No homozygous beta-catenin-deleted mice were born alive and died before embryonic day 14.5, indicating significant and irreplaceable roles of beta-catenin in embryonic heart development. Heterozygous beta-catenin-deleted mice, however, demonstrated no structural and functional abnormality. The response of heterozygous beta-catenin-deleted mice to transverse aortic constriction, however, was significantly attenuated with decreased heart weight and heart weight/body weight ratio compared to controls with intact beta-catenin genes. Hemodynamic analysis revealed that there was no difference in cardiac function between wild-type and heterozygous beta-catenin-deleted mice. On the other hand, the expression of fetal genes, beta-myosin heavy chain, atrial and brain natriuretic peptides was significantly higher in heterozygous beta-catenin-deleted mice when compared to wild-type beta-catenin mice. These results suggest that the cytoplasmic level of beta-catenin modulates hypertrophic response and fetal gene reprogramming after pressure overload.

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