Investigating molecular and cellular responses to myocardial infarction: canonical wnt activation and endothelial-to-mesenchymal transition

Abstract

This dissertation project was aimed at elucidating cellular and molecular responses to myocardial infarction. Our work identified canonical wnt signaling as a molecular pathway that is induced in the healing (granulation tissue formation) stages of myocardial infarction (MI). We identified endothelial-to-mesenchymal transition as a cellular response to MI that occurs during granulation tissue formation, coincident with canonical wnt activation. We show that canonical wnt signaling is sufficient to induce endothelial-to-mesenchymal transition in the mature vasculature. Our findings suggest that canonical wnt signaling mediates endothelial-to-mesenchymal transition to generate new blood vessels and scar-forming myofibroblasts during post-infarction granulation tissue formation. These findings suggest an intricate cellular (EndMT) and molecular (canonical wnt signaling) connection between two critical repair mechanisms with apparently opposing effects, beneficial neovascularization and detrimental fibrosis. This intrinsic link may open the opportunity to improve the course of cardiac repair post-MI by temporal and cell type-specific manipulation of canonical wnt signaling.

Approved: Professor Antonis Hatzopoulos Date: 09-02-2010