Document Detail

Left ventricular dilation in toll-like receptor 2 deficient mice after myocardial ischemia/reperfusion through defective scar formation.
MedLine Citation:
PMID:  20967453     Owner:  NLM     Status:  In-Process    
Restoration of myocardial blood flow after ischemia triggers an inflammatory response involving toll-like receptors (TLRs). TLR2(-/-)-mice show short-term advantages upon reperfusion injury as compared with WT controls. Accordingly, it has been shown that transient TLR2-blockade prior to reperfusion is associated with improved left-ventricular performance after myocardial scar formation. We present here adverse myocardial remodeling due to a chronic lack of TLR2 expression. Myocardial ischemia/reperfusion (MI/R) was surgically induced in C3HeN-mice by ligation of the left anterior descending coronary artery for 20 min, followed by 24 h or 28 days of reperfusion. TLR2(-/-)-mice and TLR2-Ab treated (T2.5) WT-mice displayed a reduction of infarct size, plasma troponin T concentrations, and leukocyte infiltration as compared with untreated controls after 24 h of reperfusion. After 28 days, however, magnetic resonance imaging revealed a marked left ventricular dilation in TLR2(-/-)-animals, which was associated with pronounced matrix remodeling characterized by reduced collagen and decorin density in the infarct scar. Our data show adverse effects on myocardial remodeling in TLR2(-/-)-mice. Although interception with TLR2 signaling is a promising concept for the prevention of reperfusion injury after myocardial ischemia, these data give cause for serious concern with respect to the time-point and duration of the potential treatment.
Jan Mersmann; Katharina Habeck; Kathrina Latsch; René Zimmermann; Christoph Jacoby; Jens W Fischer; Christian Hartmann; Jürgen Schrader; Carsten J Kirschning; Kai Zacharowski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-22
Journal Detail:
Title:  Basic research in cardiology     Volume:  106     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  89-98     Citation Subset:  IM    
Clinic of Anaesthesiology, Intensive Care Medicine, and Pain Therapy, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany.
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