The Toll-like receptor 9 ligand CPG-C attenuates acute inflammatory cardiac dysfunction.

TitleThe Toll-like receptor 9 ligand CPG-C attenuates acute inflammatory cardiac dysfunction.
Publication TypeJournal Article
Year of Publication2011
AuthorsMathur, S, Walley, KR, Boyd, JH
JournalShock
Volume36
Issue5
Pagination478-83
Date Published2011 Nov
ISSN1540-0514
KeywordsAnimals, Echocardiography, Inflammation, Lipopolysaccharides, Male, Mice, Mice, Inbred C57BL, Myocardial Infarction, Myocardial Reperfusion Injury, Myocytes, Cardiac, NF-kappa B, Oligodeoxyribonucleotides, Toll-Like Receptor 9
Abstract

Stimulation of toll-like receptor 9 (TLR9) by CpG-C containing oligonucleotides attenuates ischemic injury in the brain and liver. In this study, we investigate whether any of the three classes of CpG (A, B, or C) mitigate ischemia-induced cardiac dysfunction. We measured left ventricular ejection fraction (LVEF) in C57BL/6 mice using transthoracic echocardiography. Using LPS as an inflammatory stimulus, CpG-C was uniquely able to prevent cardiac dysfunction; its activity was confirmed through nuclear factor κB transcriptional activity assay in HL-1 cardiomyocytes. We went on to investigate CpG-C's efficacy and mechanism in the treatment of ischemia-reperfusion. Compared with baseline, no class of CpG significantly altered LVEF at 6 or 24 h; 40 mg/kg LPS induced a rapid, profound suppression of LVEF compared with baseline (26% ± 1.4% vs. 65% ± 1.4%), whereas pretreatment with CpG demonstrated that of the three classes, only CpG-C prevented the LPS -induced decrease in LVEF (51% ± 5.8%). In separate mice, 1-h ischemia followed by reperfusion of the left anterior descending artery resulted in a 7-day suppression of the LVEF (66% ± 5.2% at baseline; 46% ± 4.7% at day 1, and 46% ± 4.0% at day 7), whereas mice either pretreated with or begun on an infusion of CpG-C during the ischemia had no significant decline in LVEF. Gene expression microarray of CpG-C-stimulated cells revealed upregulation of the nuclear factor κB pathway inhibitors TNFAIP3, NFKBIA, TRIM30, and TNIP1. These may play a role in attenuation of cardiac inflammation. The TLR9 ligand CpG-C attenuates the acute inflammatory cardiac dysfunction induced by both LPS and ischemia-reperfusion of the left anterior descending artery.

DOI10.1097/SHK.0b013e31822d6442
Alternate JournalShock
PubMed ID21937956
Grant List / / Canadian Institutes of Health Research / Canada