title: Toll-like receptor 9-activation during onset of myocardial ischemia does not influence infarct extension.
abstract: OBJECTIVE
  Myocardial infarction (MI) remains a major cause of death and disability worldwide, despite available reperfusion therapies. Inflammatory signaling is considered nodal in defining final infarct size. Activation of the innate immune receptor toll-like receptors (TLR) 9 prior to ischemia and reperfusion (I/R) reduces infarct size, but the consequence of TLR9 activation timed to the onset of ischemia is not known.
  
  
  RESULTS
  The TLR9-agonist; CpG B was injected i.p. in C57BL/6 mice immediately after induction of ischemia (30 minutes). Final infarct size, as well as area-at-risk, was measured after 24 hours of reperfusion. CpG B injection resulted in a significant increase in circulating granulocytes and monocytes both in sham and I/R mice. Paradoxically, clear evidence of reduced cardiac infiltration of both monocytes and granulocytes could be demonstrated in I/R mice treated with CpG B (immunocytochemistry, myeloperoxidase activity and mRNA expression patterns). In addition, systemic TLR9 activation elicited significant alterations of cardiac inflammatory genes. Despite these biochemical and cellular changes, there was no difference in infarct size between vehicle and CpG B treated I/R mice.
  
  
  CONCLUSIONS
  Systemic TLR9-stimulation upon onset of ischemia and subsequent reperfusion does not alter final infarct size despite causing clear alterations of both systemic and cardiac inflammatory parameters. Our results question the clinical usefulness of TLR9 activation during cardiac I/R.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Ingrid Kristine
authors.initials: IK
authors.lastname: Ohm
authors.affiliation: Center for Translational Medicine, School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Maria
authors.initials: M
authors.lastname: Belland Olsen
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Katrine
authors.initials: K
authors.lastname: Alfsnes
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Marte
authors.initials: M
authors.lastname: Bliksøen
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Jonas
authors.initials: J
authors.lastname: Øgaard
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Trine
authors.initials: T
authors.lastname: Ranheim
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Ståle Haugset
authors.initials: SH
authors.lastname: Nymo
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Yangchen Dhondup
authors.initials: YD
authors.lastname: Holmen
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K.G. Jebsen Cardiac Research Center, University of Oslo, Oslo, Norway.
authors.forename: Leif Erik
authors.initials: LE
authors.lastname: Vinge
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009203:Myocardial Infarction / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D017202:Myocardial Ischemia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009841:Oligonucleotides / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000378:metabolism*
chemical_list: D009841:Oligonucleotides; D051217:Toll-Like Receptor 9; D009195:Peroxidase