Abstract 18155: Wnt10b Promotes Cardiac Functional Recovery After Infarction Through Stimulation of Coronary Vessel Formation and Cardiomyogenesis
We previously showed that the canonical Wnt signaling ligand Wnt10b is strongly induced in mouse hearts one week after infarction during the initial stages of cardiac tissue repair. Wnt10b regulates cell fate decisions in various organs, but its role in the heart is unknown. Using histological and molecular analyses, we discovered that Wnt10b is normally expressed in cardiomyocytes and stored in the intercalated discs. One week after coronary artery ligation, Wnt10b is strongly and specifically induced in cardiomyocytes surrounding the infarct zone. To determine the role of Wnt10b in cardiac repair, we generated a new mouse transgenic line to enhance the levels of endogenous Wnt10b expression in cardiomyocytes. We found that gain of Wnt10b function orchestrated a recovery phenotype characterized by robust neovascularization of the infarct zone, reduced scar size, and improved ventricular function compared to wild-type mice. Wnt10b stimulated Vascular Endothelial Growth Factor Receptor 2 (Vegfr-2) in endothelial cells and Angiopoietin-1 in smooth muscle cells through NF-kB activation. These effects coordinated endothelial growth and pericyte recruitment, thus promoting the formation of large, coronary-like blood vessels. Enhanced neovascularization and reduced fibrosis was accompanied by formation of cardiomyocyte islands within scar tissue, suggesting that Wnt10b promoted myocardial regeneration. Taken together, our results indicate that Wnt10b is a physiological regulator of coordinated formation of blood vessels and myocardial regeneration in the injured heart. Our findings could lead to novel effective strategies to optimize the inherent reparative and regenerative capacities of the heart in order to prevent the onset of heart failure after myocardial infarction.
- © 2013 by American Heart Association, Inc.