Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction.
BACKGROUND
Toll-like receptors (TLRs) are members of the interleukin-1 receptor family and transduce similar signals as interleukin-1 receptor in response to exogenous pathogens. Recent studies have demonstrated that TLRs are activated by endogenous signals, such as heat shock proteins and oxidative stress, that may contribute to ventricular remodeling after myocardial infarction. In this study, we determined whether TLR-2 was involved in cardiac remodeling after myocardial infarction.


RESULTS
Myocardial infarction was induced by surgical left anterior descending coronary artery ligation on wild-type (WT) mice and TLR-2-knockout (KO) mice. The survival rate was significantly higher in KO mice than in WT mice 4 weeks after myocardial infarction (65% versus 43%, P<0.03). Infarct size and degree of inflammatory cell infiltration in infarct area were similar between WT and KO mice. However, myocardial fibrosis in the noninfarct area of KO mice was much less than in WT mice (P<0.01) and was accompanied by reduced transforming growth factor-beta1 and collagen type 1 mRNA expressions (P<0.01 and P<0.05, respectively). Left ventricular dimensions at end diastole were smaller in KO mice than in WT mice at 1 week (P<0.05) and 4 weeks (P<0.01) after surgery. Furthermore, fractional shortening was higher (27.7+/-2.5% versus 21.2+/-2.6%, P<0.05, at 1 week, and 24.3+/-2.0% versus 16.6+/-2.5%, P<0.01, at 4 weeks) in KO mice compared with WT mice.


CONCLUSIONS
These data suggest that TLR-2 plays an important role in ventricular remodeling after myocardial infarction.
Shishido
Tetsuro
T
First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
Nozaki
Naoki
N
Yamaguchi
Seiji
S
Shibata
Yoko
Y
Nitobe
Joji
J
Miyamoto
Takuya
T
Takahashi
Hiroki
H
Arimoto
Takanori
T
Maeda
Kunihiko
K
Yamakawa
Mitsunori
M
Takeuchi
Osamu
O
Akira
Shizuo
S
Takeishi
Yasuchika
Y
Kubota
Isao
I
D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009504:Neutrophils / Q000473:pathology; D009929:Organ Size; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D020257:Ventricular Remodeling / Q000502:physiology*
D024042:Collagen Type I; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C508961:Tgfb1 protein, mouse; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1