Cardiac Progenitor Cells Engineered With βARKct Have Enhanced β-Adrenergic Tolerance
Year: 2013
Type: article
Abstract: Stem cell survival and retention in myocardium after injury following adoptive transfer is low. Elevated catecholamine levels coinciding with myocardial injury adversely affect cardiac progenitor cell (CPC) survival. The G protein-coupled receptor kinase 2 (GRK2)-derived inhibitory peptide, βARKct, enhance myocyte contractility, survival, and normalize the neurohormonal axis in failing heart, however salutary effects of βARKct on CPC survival and proliferation are unknown. Herein, we investigated whether the protective effects of βARKct expression seen in the failing heart relate to CPCs. Modified CPCs expressing βARKct enhanced AKT/eNOS signaling through protective β2-adrenergic receptors (β2-ARs). In addition, to the actions of βARKct expression on β2- AR signaling, pharmacologic inhibition of GRK2 also increased β2-AR signaling in nonengineered CPCs (lacking βARKct) but had limited effects in βARKct engineered CPCs providing evidence for the strength of the βARKct in inhibiting GRK2 in these cells. Increased proliferation and metabolic activity were observed in βARKct-engineered CPCs following catecholamine stimulation indicating improved adrenergic tolerance. βARKct modification of CPCs increased survival and proliferation following adoptive transfer in an acute myocardial infarction model concomitant with increased expression of β-AR. Thus, βARKct engineering of CPCs promotes survival and proliferation of injected cells following myocardial infarction, which includes improved β-adrenergic tolerance essential for stem cell survival.
Source: Molecular Therapy
DOI: 10.1038/mt.2013.200
Institutions: San Diego State University, Temple University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: Antagonism of myocardial aging and senescence with Pim-1 kinase, Restoring Mycocardial Healing, G246043078, Targeting GRK2 in the Heart, G3287535790, The effect of high-fat low-carbon diet on cardiac function and metabolism, Stem Cell Signaling in the Pathologically Challenged Myocardium, Control of Cardiac Growth by Ca2+Dependent Phosphorylation of Histones, Inducible Notch improves progenitor cell repair of damaged heart, Nucleolar disruption in response to cardiomyopathic stress and injury, Engineering Cardiac Progenitor Cells to Enhance Myrocardial Regengeration, Beta-adrenergic signaling: double edged sword of myocardial repair, b1AR-mediated EGFR transactivation in the heart, Targeting GRK2 (BARK1) in Heart Failure, Improving Cardiac Function After Myocardial Infarction, Cardioprotection by optimizing mTOR activity, G7689479548, Regulation of Signal Transduction to Treat Heart Failure, GRK and b-Arrestin Signaling in Cardiac Regeneration, Novel Mechanisms and Therapies in Heart Failure
OpenAlex ID: W2002078472