Wnt/β-Catenin Signaling during Cardiac Development and Repair
Abstract
:1. Introduction
2. Wnt Signaling during Cardiogenesis
3. Wnt Signaling during Cardiac Repair
References | Target | Treatment/modulation | Wnt/β-cat | Timing | Outcome |
---|---|---|---|---|---|
[61] | Fzd-1/Fzd-2 | Peptidergic Fzd-1/Fzd-2 antagonist UM206 | ↓ | 0 or 14d post-MI (similar results) | Reduction of infarct expansion and increased repair in infarct area |
[59] | Sfrp2 | Recombinant Sfrp2 injection | ↓ | Injection 2d post-MI | Reduced fibrosis and improved LVEF |
[60] | Sfrp2 | KO mice | ↑ | - | Reduced fibrosis and significantly higher LVEF compared to controls |
[62] | Sfrp1 | αMHC-specific Sfrp1 overexpression with doxycycline inducible repression | ↓ | Overexpression/repression (1wk prior to MI) | Ischemic preconditioning caused improved outcomes after MI due to GSK-3β inhibition, but this effect was diminished in Sfrp1-overexpressing CM |
[58] | Sfrp1 | Overexpression of Sfrp1 | ↓ | - | Reduction of infarct size, fibrosis and improved cardiac function (7 d or 30 d post-MI) |
[64] | GSK-3α | KO mice | ↑ | - | Increased mortality (10 d post-MI), more LV dilatation, dysfunction, hypertrophy, fibrosis and heart failure (8 weeks post-MI) and increased apoptosis in border zone (2 d post-MI) in KO mice |
[65] | GSK-3β | KO mice (tamoxifen inducible) | ↑ | KO at 3d post-MI | Improved LVEF and LV dilatation with less hypertrophy post-MI in GSK-3β KO mice (8 weeks post-MI) |
[63] | GSK-3 | KO mice | ↑ | - | No functional difference between GSK-3 KO mice and controls |
[66] | GSK-3β | Inhibitors (Lithium/SB216763) | ↑ | Directly after MI | GSK-3β inhibition mimicked ischemic precondition, resulting in less apoptotic cardiomyocytes and increased capillary density |
[69] | β-catenin | Nuclear inhibitor (ICG-001) | ↓ | Directly after MI for 10d | Improved LVEF (10 d post-MI) and increased EMT in epicardial cells in treated mice |
[6] | β-catenin | Downregulation (tamoxifen inducible) in cardiac fibroblasts | ↓ | 10d prior to MI | Increased left ventricular dilatation (8 d post-MI) and decreased cardiac fibroblast proliferation in vitro |
[68] | β-catenin | αMHC specific depletion orstabilization of β-catenin | ↓/↑ | - | Upregulation of fetal gene program (GATA4, Tbx5) and improved MI outcomes (LVEF and mortality) in β-catenin depleted animals compared to stabilization |
[67] | β-catenin | Overexpression of β-catenin | ↑ | Directly after MI | Decreased left ventricular dilatation, increased fractional shortening and decreased apoptosis compared to controls (7 d post-MI) |
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Buikema, J.W.; Zwetsloot, P.-P.M.; Doevendans, P.A.; Domian, I.J.; Sluijter, J.P.G. Wnt/β-Catenin Signaling during Cardiac Development and Repair. J. Cardiovasc. Dev. Dis. 2014, 1, 98-110. https://doi.org/10.3390/jcdd1010098
Buikema JW, Zwetsloot P-PM, Doevendans PA, Domian IJ, Sluijter JPG. Wnt/β-Catenin Signaling during Cardiac Development and Repair. Journal of Cardiovascular Development and Disease. 2014; 1(1):98-110. https://doi.org/10.3390/jcdd1010098
Chicago/Turabian StyleBuikema, Jan W., Peter-Paul M. Zwetsloot, Pieter A. Doevendans, Ibrahim J. Domian, and Joost P. G. Sluijter. 2014. "Wnt/β-Catenin Signaling during Cardiac Development and Repair" Journal of Cardiovascular Development and Disease 1, no. 1: 98-110. https://doi.org/10.3390/jcdd1010098