Cardiac Specific Haploin sufficiency of ?-Catenin Attenuates Cardiac Hypertrophy But Enhances Fetal Gene Expression in Response to Aortic Constriction
Jiaxiang Qu¹, Jibin Zhou¹, Xian Ping Yi^1,2, Baojun Dong¹, Hanqiao Zheng¹, Lisa M. Miller¹, Xuejun Wang¹, Michael D. Schneider⁴, Faqian Li^1
1Sanford Research/USD, Cardiovascular Research Institute, The University of South Dakota and Sanford Health, Sioux Falls, SD, ²Department of Pathology, Zhongshan University the Fifth Affiliated Hospital, P. R. China., ⁴Department of Medicine, Department of Cell Biology, and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas.

• > In addition to its role in cell adhesion, ß-catenin is an important signaling molecule in the Wnt/Wingless signaling pathway. Recent studies have indicated that ß-catenin is stabilized by hypertrophic stimuli and may regulate cardiac hypertrophic responses. To explore the role and requirement of ß-catenin in cardiac development and hypertrophy, we deleted the ß-catenin gene specifically in cardiac myocytes by crossing loxP-floxed ß-catenin mice with transgenic mice expressing a Cre recombinase under the control of the a-myosin heavy chain promoter. No homozygous ß-catenin deleted mice were born alive and died before embryonic day 14.5, indicating significant and irreplaceable roles of ß-catenin in embryonic heart development. Heterozygous ß-catenin deleted mice, however, demonstrated no structural and functional abnormality. The response of heterozygous ß-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 ß-catenin genes. Hemodynamic analysis (Vevo 660 micro-ultrasound, VisualSonics) revealed that there was no difference in cardiac function between wild type and heterozygous ß-catenin deleted mice. On the other hand, the expression of fetal genes, ß-myosin heavy chain, atrial and brain natriuretic peptides was significantly higher in heterozygous ß-catenin deleted mice when compared to wild type ß-catenin mice. These results suggest that the cytoplasmic level of ß-catenin modulates hypertrophic response and fetal gene reprogramming after pressure overload.