P. Noemi, M. Zimmermann, D. Pils, G. Maurer, M. Gyöngyösi, H.J. Ankersmit – Medical University of Vienna – Vienna – Austria
Background: We have investigated the effect of catheter-based endomyocardial injections of APOSEC (secretome of apoptotic peripheral white blood cells) on porcine chronic post-infarction (MI) left ventricular (LV) dysfunction and gene expression profile compared with placebo.
Methods and results: Closed-chest reperfused MI was induced by 90-min occlusion followed by reperfusion of the mid LAD (day 0). At day 30 the animals were randomized and received either porcine APOSEC (n=8) or placebo Medium (n=8) injected into the border zone of MI using 3D NOGA percutaneous intramyocardial guidance. At day 60 tissue samples were collected. Gene expression profiling of the infarct core, border zone and normal myocardium was performed using microarray analysis, confirmed by quantitative real-time PCR. Gene array revealed significant dowregulation of caspase-1 and other inflammatory genes in the APOSEC-affected areas. PCR showed higher levels of expression of myogenic factor Mefc2 (p<0.05) with downregulated caspase-3 (p<0.05) in the APOSEC-pigs.
Conclusions: Overexpression of MEF2c and repression of caspase is related to decrease in infarct size and improved cardiac function in secretome-treated animals. The altered gene-expression 1-month post APOSEC-treatment suggests a long-acting effect of injected paracrine factors.