Left ventricular dilation in toll-like receptor 2 deficient mice after myocardial ischemia/reperfusion through defective scar formation.
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.
Clinic of Anaesthesiology, Intensive Care Medicine, and Pain Therapy, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany.
Jan
J
Mersmann
Katharina
K
Habeck
Kathrina
K
Latsch
René
R
Zimmermann
Christoph
C
Jacoby
Jens W
JW
Fischer
Christian
C
Hartmann
Jürgen
J
Schrader
Carsten J
CJ
Kirschning
Kai
K
Zacharowski
D000818:Animals; D058578:Biglycan / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D058575:Decorin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D009205:Myocarditis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*; D020257:Ventricular Remodeling; D014945:Wound Healing
D058578:Biglycan; D058575:Decorin; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D003094:Collagen