| First Author | Feridooni T | Year | 2017 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 312 |
| Issue | 5 | Pages | H919-H931 |
| PubMed ID | 28283550 | Mgi Jnum | J:241640 |
| Mgi Id | MGI:5903325 | Doi | 10.1152/ajpheart.00425.2016 |
| Citation | Feridooni T, et al. (2017) Effects of beta-adrenergic receptor drugs on embryonic ventricular cell proliferation and differentiation and their impact on donor cell transplantation. Am J Physiol Heart Circ Physiol 312(5):H919-H931 |
| abstractText | beta-Adrenergic receptors (beta-ARs) and catecholamines are present in rodents as early as embryonic day (E)10.5. However, it is not known whether beta-AR signaling plays any role in the proliferation and differentiation of ventricular cells in the embryonic heart. Here, we characterized expression profiles of beta-AR subtypes and established dose-response curves for the nonselective beta-AR agonist isoproterenol (ISO) in the developing mouse ventricular cells. Furthermore, we investigated the effects of ISO on cell cycle activity and differentiation of cultured E11.5 ventricular cells. ISO treatment significantly reduced tritiated thymidine incorporation and cell proliferation rates in both cardiac progenitor cell and cardiomyocyte populations. The ISO-mediated effects on DNA synthesis could be abolished by cotreatment of E11.5 cultures with either metoprolol (a beta1-AR antagonist) or ICI-118,551 (a beta2-AR antagonist). In contrast, ISO-mediated effects on cell proliferation could be abolished only by metoprolol. Furthermore, ISO treatment significantly increased the percentage of differentiated cardiomyocytes compared with that in control cultures. Additional experiments revealed that beta-AR stimulation leads to downregulation of Erk and Akt phosphorylation followed by significant decreases in cyclin D1 and cyclin-dependent kinase 4 levels in E11.5 ventricular cells. Consistent with in vitro results, we found that chronic stimulation of recipient mice with ISO after intracardiac cell transplantation significantly decreased graft size, whereas metoprolol protected grafts from the inhibitory effects of systemic catecholamines. Collectively, these results underscore the effects of beta-AR signaling in cardiac development as well as graft expansion after cell transplantation.NEW & NOTEWORTHY beta-Adrenergic receptor (beta-AR) stimulation can decrease the proliferation of embryonic ventricular cells in vitro and reduce the graft size after intracardiac cell transplantation. In contrast, beta1-AR antagonists can abrogate the antiproliferative effects mediated by beta-AR stimulation and increase graft size. These results highlight potential interactions between adrenergic drugs and cell transplantation. |
