The Origin and Stimuli Implicated in the Expression of Nestin Cardiac Myocyte- like Cells in the Ischemic Heart

Studies from our lab demonstrated that scar formation and healing was associated with the appearance of nestin (+) cardiac myocyte-like cells predominantly at the peri-infarct region. The focus of the present study was to identify the underlying mechanism(s) (e.g. hypoxia, neurohormones) implicated in their recruitment and their cellular origin. The presence of these cells was detected as early as 1-week post-myocardial infarction (MI) and persisted 9 months after complete coronary artery ligation. Furthermore, nestin (+) cardiac myocyte-like cells were also detected in the infarcted human heart. Hypoxia represents a predominant stimulus following MI, however the exposure of normal rats to a hypoxic environment failed to promote the re-appearance of nestin (+) cardiac myocyte-like cells. By contrast, the infusion of the non-selective β-adrenergic agonist isoproterenol (ISO) in the normal adult Sprague-Dawley rat increased nestin expression in the left ventricle and was associated with the reappearance of nestin (+) cardiac myocyte-like cells. However, the reappearance of nestin (+) cardiac myocyte-like cells may not represent a direct effect but was apparently secondary to cardiac myocyte necrosis mediated by isoproterenol. Lastly, we identified a subpopulation of nestin-immunoreactive cells in the normal rat heart that coexpressed cardiac progenitor cell markers Nkx-2.5 and GATA-4. This subpopulation of nestin/Nkx-2.5/GATA-4 cells may represent the progenitor pool that differentiates to a nestin (+) cardiac myocyte-like cell following an ischemic insult.