Résumé
Endogenous progenitor cells may participate in cardiac repair after a myocardial infarction. The beta adrenergic pathway has been proposed to induce proliferation and migration of progenitor cells. However the mechanisms have not yet been clarified.
The mechanism underlying beta adrenergic signaling on endogenous c-kit+/CD45 – cardiac cells was investigated by inducing myocardial infarction in adult mice. Hearts were dissociated and flow cytometry analysis demonstrated that one week after ligation, the percentage of c-kit+/ CD45 – cells expressing beta 1 or beta 2 adrenergic receptor was significantly increased (88.1±3% and 106.8±36.5% increase compared to sham respectively). Flow cytometry studies on cultured cardiac c-kit+/CD45 – cells confirmed increased beta 1 and 2 adrenergic receptor expression in response to stress conditions, specifically hypoxia (5%) or serum starvation. Interestingly, stress conditions altered localization of the beta 2 adrenergic receptor by increasing membrane expression. The beta 2 adrenergic receptor signaling pathway was stimulated in adult sham mice with the agonist fenoterol (0.25mg/kg/day) administered in drinking water. Seven days after treatment the mice and non-treated controls were sacrificed and progenitor cells were measured by flow cytometry in the heart and blood. Fenoterol increased the proliferation and percentage of c-kit+/CD45 – cells in the heart (123.3±86.2% and 70.9±44.6% increase compared to control respectively). Fenoterol treatment also elevated levels of circulating endothelial progenitor cells (158.5±87.9% compared to control) and c-kit/CD45 – cells (70.6±33.5% increase) in the peripheral blood.
Beta adrenergic receptor expression is increased after coronary ligation in vivo and in stress conditions in vitro. A beta 2 adrenergic receptor agonist may be used to improve endogenous cardiac repair through the activation of progenitor cells.
The author hereby declares no conflict of interest