Modulation of Cx43 Expression and Targeting of the Myocardial Scar: Impact on Cell Fate, Scar Formation, and Electrical Vulnerability Post-Myocardial Infarction

Project Summary

This project explores novel approaches aimed at preventing post-myocardial infarction ventricular tachyarrhythmias by increasing the electrical coupling of the native myocardium with the myocardial scar. This builds on prior work showing anti-arrhythmic effects of grafting connexin-43 (Cx43) expressing cells in left ventricular lesions. P14 will generate Cx43 overexpression models, study changes in cardiomyocytes and non-myocytes cell biology upon Cx43 overexpression and explore whether Cx43 (over-)expression in fibroblasts, myofibroblasts or cardiomyocytes confers protection from ventricular tachycardia. The project will also develop technologies for efficient and site-specific gene targeting, using magnetic nanoparticle/ virus complexes in combination with magnetic steering to improve gene expression in the myocardial scar and to reduce side-effects due to inefficient or nonspecific targeting.