The Role of Beta-Adrenergic Signaling in Cardiac P.. (Heart Betas)
The Role of Beta-Adrenergic Signaling in Cardiac Progenitor Cell Activation after Myocardial Infarction
Start date: 14 Apr 2015,
End date: 13 Apr 2017
Cardiovascular diseases are a leading cause of mortality in the industrialized world with myocardial infarction (MI) being one of the common pathological events. Cardiac progenitor cells (CPC) are a progenitor cell population within the myocardium and are activated after MI to proliferate, migrate to the infarct site, and participate in cardiac regeneration. CPC are a current therapeutic target to diminish cardiac injury after a MI. After a MI, the beta-adrenergic system gets activated due to excessive concentrations of catecholamines accumulating in the myocardium. Interestingly, beta-2 adrenergic signaling has been suggested to promote CPC proliferation. It is currently unknown whether resident CPC could be affected by β-adrenergic signaling therapies. We therefore propose the general hypothesis that beta2-adrenergic receptor signaling after a MI favors the activation of endogenous CPC. We will use a mouse model of MI to evaluate the activation of CPC after treatment with beta-adrenergic agonists/antagonists. CPC will be analyzed by flow cytometry and immunohistochemistry. Cardiac outcomes (infarct size and arrhythmic events) will be correlated to the activation of the CPC. We will further investigate the hypothesis that beta2-adrenergic signaling mediates CPC activation through the regulation of intracellular calcium. We will treat murine and human CPC with beta-adrenergic agonists/antagonists and examine changes in intracellular calcium flux. We will correlate the effect of beta-adrenergic signaling on CPC proliferation and migration in vitro to calcium handling. Validation of our hypothesis would begin to dissect the natural molecular signals that are an integral part of myocardial healing.
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