297 Non-HLA Antibody Screening after Heart Transplantation Identifies High Risk for Cardiac Allograft Vasculopathy
| Autor: | Hartmuth B. Bittner, Duska Dragun, Sara Klein, S. von Salisch, Markus J. Barten, Stefan Dhein, J. Garbade, Friedrich-Wilhelm Mohr, Maja-Theresa Dieterlen |
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| Rok vydání: | 2012 |
| Předmět: |
Pulmonary and Respiratory Medicine
Heart transplantation Transplantation medicine.medical_specialty Cell signaling Microarray business.industry Microarray analysis techniques medicine.medical_treatment Molecular biology Immune system Internal medicine medicine Cardiology Lung transplantation Surgery Cardiology and Cardiovascular Medicine business Gene |
| Zdroj: | The Journal of Heart and Lung Transplantation. 31:S107 |
| ISSN: | 1053-2498 |
| DOI: | 10.1016/j.healun.2012.01.305 |
| Popis: | lungs prior to transplantation results in outcomes similar to that of contemporaneous lung transplantation. The underlying mechanism for this effect remains to be identified. We performed a time-course microarray analysis on rejected donor lungs subjected to 12 h of EVLP to further investigate the mechanism. Methods and Materials: Rejected human lungs were subjected to 12 h of EVLP(n 6). Tissue biopsies taken at time zero and every three hours hence were snap-frozen and stored at 80C, resulting in a total of 30 samples. RNA was extracted from all samples (RIN 7) and utilized for microarray (Affy U133plus2) analysis. Preprocessing was performed using the PLIER method, followed by time-course analysis and clustering using the STEM method. Gene ontology was utilized on the resulting geneclusters to identify the enriched functional modules and pathways. Results: About 6% of all genes showed at least 2-fold variability across the time-course (2013 genes). Of these, about two-thirds (1356/2013) were assigned by STEM to a statistically significant cluster, indicating a coherent temporal trend. More genes showed decreasing expression (58.1%; 788 genes) than increasing expression (33.8%; 458 genes). A small fraction showed transient changes (8.1%; 110 genes). Down-regulated genes were enriched for genes involved in immune response (p 0.001), for oxidoreductases(p 0.002), and for genes involved in the defense response(p 0.016) and include genes such as CCL5, CCR2, CCR5, CCL17, TLR7, and TLR5. In contrast, genes which increased in expression during EVLP were enriched for those involved in signal transduction (p 0.001) and include genes such as SMAD3, HMGA1, and FOXE3. Conclusions: During EVLP, genes involved in the immune and inflammatory response become downregulated over time. In contrast, genes involved in the regulation of cellular signaling become upregulated during EVLP. These changes may pre-condition the lungs to better tolerate reperfusion post-transplantation. |
| Databáze: | OpenAIRE |
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