| Title: |
Synthetic CpG oligonucleotides induce a genetic profile ameliorating murine myocardial I/R injury |
| Authors: |
Hilbert, Tobias; Markowski, Paul; Frede, Stilla; Boehm, Olaf; Knuefermann, Pascal; Baumgarten, Georg; Hoeft, Andreas; Klaschik, Sven |
| Source: |
Journal of Cellular and Molecular Medicine ; volume 22, issue 7, page 3397-3407 ; ISSN 1582-1838 1582-4934 |
| Publisher Information: |
Wiley |
| Publication Year: |
2018 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
We previously demonstrated that pre‐conditioning with CpG oligonucleotide ( ODN ) 1668 induces quick up‐regulation of gene expression 3 hours post‐murine myocardial ischaemia/reperfusion (I/R) injury, terminating inflammatory processes that sustain I/R injury. Now, performing comprehensive microarray and biocomputational analyses, we sought to further enlighten the “black box” beyond these first 3 hours. C57 BL /6 mice were pretreated with either CpG 1668 or with control ODN 1612, respectively. Sixteen hours later, myocardial ischaemia was induced for 1 hour in a closed‐chest model, followed by reperfusion for 24 hours. RNA was extracted from hearts, and labelled cDNA was hybridized to gene microarrays. Data analysis was performed with BRB ArrayTools and Ingenuity Pathway Analysis. Functional groups mediating restoration of cellular integrity were among the top up‐regulated categories. Genes known to influence cardiomyocyte survival were strongly induced 24 hours post‐I/R. In contrast, proinflammatory pathways were down‐regulated. Interleukin‐10, an upstream regulator, suppressed specifically selected proinflammatory target genes at 24 hours compared to 3 hours post‐I/R. The IL 1 complex is supposed to be one regulator of a network increasing cardiovascular angiogenesis. The up‐regulation of numerous protective pathways and the suppression of proinflammatory activity are supposed to be the genetic correlate of the cardioprotective effects of CpG 1668 pre‐conditioning. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1111/jcmm.13616 |
| Availability: |
https://doi.org/10.1111/jcmm.13616; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fjcmm.13616; https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.13616; https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jcmm.13616 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.10682D2D |
| Database: |
BASE |