(229) - Metabolic Status Determines the Efficacy of CD34+ Stem Cell Therapy in Patients With Non-Ischemic Dilated Cardiomyopathy

Abstract

s S91 (SFN) by i.p. 1 day prior to surgery to induce Nrf2, with saline as vehicle control (n= 6 per group). After 2 hours of cold ischemia, donor hearts were transplanted into the recipients. Just after transplant, recipients received an additional single injection of SFN or saline. Following 24 hours of reperfusion, echocardiography was performed and donor hearts were harvested. Superoxide dismutase-2 (SOD2) and Caspase-3 activities were measured as markers of the Nrf2 pathway downstream enzyme and apoptosis respectively. P65 and phosphorylated P65 were measured by Western immunoblotting to assess NF-kB activation. Results: Compared to WT-Saline, KO-Saline demonstrated lower SOD2, increased Caspase-3, and increased P65 expression and phosphorylation. Among WT donors, SFN treatment rescued SOD2, decreased Caspase-3, and inhibited P65 phosphorylation compared to saline treatment. These SFN effects were absent on KO donors (Figure A). Echocardiography of donor hearts showed that the fractional area change (FAC) was significantly higher in WT-SFN than WT-Saline. KO-Saline and KO-SFN displayed similarly lower FAC than WT donors (Figure B). Conclusion: Our results suggest the anti-inflammatory potential of Nrf2 through inhibition of NF-kB activity during IRI. The Nrf2 pathway may be a promising pharmacological target to mitigate IRI-mediated inflammation, apoptosis, and impaired cardiac function through the anti-inflammatory property as well as its anti-oxidant nature in heart transplantation.