Inducible Overexpression of Connexin 43 in Cardiac Myofibroblasts to Mitigate Postinfarct Electrical Vulnerability

Background: Upon myocardial infarction (MI), the incidence of severe ventricular arrhythmias (VT) originating from the border zone (BZ) and/or the scar is strongly increased. This might be due to differences in conduction rates related to altered expression of the gap junction (GJ) protein Cx43 and the onset of re-entry events. Migrating and resident (myo-)fibroblasts (mFB) play a key role in post-MI scar formation, but poorly express Cx43 and cannot compensate the loss of functional GJ. To restore conduction inhomogeneities between BZ, scar area and native myocardium and investigate the consequences on cell viability, lesion size and VT incidence, we generated a transgenic mouse model enabling inducible overexpression of Cx43 in mFB of the scar.