Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Pavo, N; Zimmermann, M; Pils, D; Mildner, M; Petrási, Z; Petneházy, Ö; Fuzik, J; Jakab, A; Gabriel, C; Sipos, W; Maurer, G; Gyöngyösi, M; Ankersmit, HJ.
Long-acting beneficial effect of percutaneously intramyocardially delivered secretome of apoptotic peripheral blood cells on porcine chronic ischemic left ventricular dysfunction.
Biomaterials. 2014; 35(11): 3541-3550.
Doi: 10.1016/j.biomaterials.2013.12.071
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- Co-Autor*innen der Med Uni Graz
- GABRIEL Christian
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- Abstract:
- The quantity of cells with paracrine effects for use in myocardial regeneration therapy is limited. This study investigated the effects of catheter-based endomyocardial delivery of secretome of 2.5 × 10(9) apoptotic peripheral blood mononuclear cells (APOSEC) on porcine chronic post-myocardial infarction (MI) left ventricular (LV) dysfunction and on gene expression. Closed-chest reperfused MI was induced in pigs by 90-min occlusion followed by reperfusion of the mid-LAD (day 0). At day 30, animals were randomized to receive porcine APOSEC (n = 8) or medium solution (control; n = 8) injected intramyocardially into the MI border zone using 3D NOGA guidance. At day 60, cardiac MRI with late enhancement and diagnostic NOGA (myocardial viability) were performed. Gene expression profiling of the infarct core, border zone, and normal myocardium was performed using microarray analysis and confirmed by quantitative real-time PCR. Injection of APOSEC significantly decreased infarct size (p < 0.05) and improved cardiac index and myocardial viability compared to controls. A trend towards higher LV ejection fraction was observed in APOSEC vs. controls (45.4 ± 5.9% vs. 37.4 ± 8.9%, p = 0.052). Transcriptome analysis revealed significant downregulation of caspase-1, tumor necrosis factor and other inflammatory genes in APOSEC-affected areas. rtPCR showed higher expression of myogenic factor Mefc2 (p < 0.05) and downregulated caspase genes (p < 0.05) in APOSEC-treated pigs. In conclusion, overexpression of MEF2c and repression of caspase was related to decreased infarct size and improved cardiac function in secretome-treated animals. Altered gene expression 1-month post-APOSEC treatment proved the long-acting effects of cell-free therapy with paracrine factors. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Administration, Cutaneous -
- Animals -
- Apoptosis - genetics
- Blood Proteins - secretion
- Chronic Disease -
- Gene Expression Regulation -
- Hemodynamics -
- Leukocytes, Mononuclear - secretion Leukocytes, Mononuclear - transplantation
- Magnetic Resonance Imaging -
- Myocardial Infarction - pathology Myocardial Infarction - physiopathology Myocardial Infarction - therapy
- Myocardial Ischemia - genetics Myocardial Ischemia - pathology Myocardial Ischemia - physiopathology Myocardial Ischemia - therapy
- Neovascularization, Physiologic -
- Oligonucleotide Array Sequence Analysis -
- Proto-Oncogene Proteins c-kit - metabolism
- Reverse Transcriptase Polymerase Chain Reaction -
- Sus scrofa -
- Ventricular Dysfunction, Left - complications Ventricular Dysfunction, Left - pathology Ventricular Dysfunction, Left - physiopathology Ventricular Dysfunction, Left - therapy
- Find related publications in this database (Keywords)
- Cell-free regeneration therapy
- Gene expression
- Immunomodulation
- Myocardial infarction
- Remodeling
- Animal model