Cardiac-specific haploinsufficiency of β-catenin attenuates cardiac hypertrophy but enhances fetal gene expression in response to aortic constriction

Jiaxiang Qu, Jibin Zhou, Xian Ping Yi, Baojun Dong, Hanqiao Zheng, Lisa M. Miller, Xuejun Wang, Michael D. Schneider, Faqian Li

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)319-326
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume43
Issue number3
DOIs
StatePublished - Sep 1 2007

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Keywords

  • Aortic constriction
  • Cardiac remodeling
  • Catenin
  • Heart
  • Hypertrophy
  • Pressure overload

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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