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Postconditioning with a CpG containing Oligodeoxynucleotide ameliorates myocardial infarction in a murine closed-chest model.
MedLine Citation:
PMID:  25445440     Owner:  NLM     Status:  Publisher    
AIMS: Toll-like receptor (TLR)9 ligand CpG-oligodeoxynucleotide (CpG-ODN) exerts preconditioning in myocardial ischemia/reperfusion. We hypothesized a postconditioning effect of CpG-ODN in a murine closed-chest model of myocardial infarction.
MATERIALS AND METHODS: C57BL/6 (12weeks, male, WT) mice were instrumented at the left anterior descending artery, then allowed 5d of recovery before 30min ischemia. Treatments comprised: 1) PBS: 250μl phosphate buffer solution intraperitoneally 5min before reperfusion and 2) IPC (ischemic postconditioning): 3 twenty-second reperfusion and occlusion episodes at the end of ischemia 3) CpG-ODN: 1668 thioate 0.2μmol/kg BW intraperitoneally 5min before reperfusion. Infarct size was assessed via triphenyltetrazolium chloride (TTC) staining after 2 and 24h reperfusion. Myocardial mRNA-expression of cytokines was measured using real-time PCR after 2h reperfusion. Phosphatidylinositol-3 kinase (PI3K)-inhibitor wortmannin was injected intraperitoneally in WT 15min before postconditioning and PBS in each group. Cardiac function in WT was assessed with a left-ventricular pressure-volume catheter at 24h reperfusion.
KEY FINDINGS: Following 30min ischemia and 2h reperfusion, infarct size was diminished by 90% in WT postconditioned with CpG-ODN (2.4±1.55 IS/AAR%) and IPC (1.98±1.03 IS/AAR%) compared to PBS mice (23.2±3.97 IS/AAR%). Infarct size increased following 24h reperfusion but the differences remained robust. Expression of TNF-α and IL-10 was increased in CpG-ODN. Wortmannin abolished the postconditioning effect of CpG-ODN and IPC. Ejection fraction and preload-recruitable stroke work were significantly greater in CpG-ODN mice.
SIGNIFICANCE: CpG-ODN confers postconditioning via activation of TLR9. Cardiac function is preserved following CpG-ODN postconditioning. The PI3K -inhibitor wortmannin attenuates CpG-ODN postconditioning.
Se-Chan Kim; Shuijing Wu; Xiangming Fang; Jens Neumann; Lars Eichhorn; Grigorij Schleifer; Olaf Boehm; Rainer Meyer; Stilla Frede; Andreas Hoeft; Georg Baumgarten; Pascal Knuefermann
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-29
Journal Detail:
Title:  Life sciences     Volume:  119     ISSN:  1879-0631     ISO Abbreviation:  Life Sci.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-8     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Inc. All rights reserved.
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