Key result
H2O2 preconditioning of cardiac progenitor cells cuts in vitro apoptosis ~45% and improves post-I/R function.
Answers are grounded in this paper and cite their sources.
There are a limited number of therapies available to prevent heart failure following myocardial infarction. One novel therapy that is currently being pursued is the implantation of cardiac progenitor cells (CPCs); however, their responses to oxidative stress during differentiation have yet to be elucidated. The objective of this study was to determine the effect of hydrogen peroxide (H2O2) treatment on CPC differentiation in vitro, as well as the effect of H2O2 preconditioning before implantation following ischemia-reperfusion (I/R) injury. CPCs were isolated and cloned from adult rat hearts, and then cultured in the absence or presence of H2O2 for 2 or 5 days. CPC survival was assessed with Annexin V, and cellular differentiation was evaluated through mRNA expression for cardiogenic genes. We found that 100 μM H2O2 decreased serum withdrawal-induced apoptosis by at least 45% following both 2 and 5 days of treatment. Moreover, 100 μM H2O2 treatment for 2 days significantly increased endothelial and smooth muscle markers compared to time-matched untreated CPCs. However, continued H2O2 treatment significantly decreased these markers. Left ventricular cardiac function was assessed 28 days after I/R and I/R with the implantation of Luciferase/GFP(+) CPCs, which were preconditioned with 100 μM H2O2 for 2 days. Hearts implanted with Luciferase/GFP(+) CPCs had significant improvement in both positive and negative dP/dT over I/R. Furthermore, cardiac fibrosis was significantly decreased in the preconditioned cells versus both I/R alone and I/R with control cells. We also observed a significant increase in endothelial cell density in the preconditioned CPC hearts compared to untreated CPC hearts, which also coincided with a higher density of Luciferase(+) vessels. These findings suggest that preconditioning of CPCs with H2O2 for 2 days stimulates neoangiogenesis in the peri-infarct area following I/R injury and could be a viable therapeutic option to prevent heart failure.
No takes yet. Share an insight, caveat, or question.
Pendergrass et al. (2013) studied Myocardial ischemia-reperfusion (I/R) injury. Implantation of H2O2-preconditioned cardiac progenitor cells (CPCs) vs. Untreated CPCs or ischemia-reperfusion injury alone was evaluated on Left ventricular cardiac function (positive and negative dP/dT), cardiac fibrosis, neoangiogenesis, and in vitro CPC survival/differentiation (≥45% reduction in serum withdrawal-induced apoptosis in vitro). Preconditioning cardiac progenitor cells with 100 μM H2O2 reduced apoptosis by ≥45% in vitro and significantly improved LV dP/dT, reduced fibrosis, and increased vessel density at 28 days post-I/R.
Synapse has enriched 10 related papers. Consider them for comparative context: