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 journalArticlepeer-review

49 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 2007
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. Rolf Kemler for generously providing his mouse model to the scientific community. The project described was supported by Grant Number P20 RR017662 (F Li and XJ Wang) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and “Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH.” This work was also supported by the National Institute of Health grant HL72166 (XJ Wang) and the South Dakota Health Research Foundation, which is a partnership between the University of South Dakota School of Medicine and Sanford Health. XP Yi, a visiting scholar from China, was partly supported by the National Natural Science Foundation of China, 30470696.

Keywords

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

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