Published online before print December 1, 2003, doi: 10.1161/01.CIR.0000101921.93016.1C
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(Circulation. 2003;108:2905.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Toll-Like Receptor-2 Modulates Ventricular Remodeling After Myocardial Infarction
From the First Department of Internal Medicine (T.S., N.N., Y.S., J.N., T.M., H.T., T.A., Y.T., I.K.) and First Department of Pathology (K.M., M.Y.), Yamagata University School of Medicine, Yamagata; Sagae City Hospital, Sagae (S.Y.); and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka (O.T., S.A.), Japan.
Correspondence to Yasuchika Takeishi, MD, PhD, First Department of Internal Medicine, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, Japan 990-9585. E-mail takeishi{at}med.id.yamagata-u.ac.jp
Received December 18, 2002; de novo received June 11, 2003; revision received August 7, 2003; accepted August 8, 2003.
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.
Methods and 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-ß1 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.
Key Words: receptors • remodeling • myocardial infarction • heart failure
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