Abstract 13037: Tenascin-c Modulates Inflammatory Response and Aggravate Ventricular Remodeling After Myocardial Infarction in Mice Model
Tenascin-C (TN-C), an extracellular matrix glycoprotein, transiently appeared in myocardial tissue after acute myocardial infarction (AMI). We have previously reported that AMI patients with higher serum TN-C levels had worse long-term prognosis, suggesting TN-C may play important roles during the development of ventricular remodeling. However, the biological function of TN-C in ventricular remodeling is not fully understood. In this study, using TN-C knock-out(KO) mice, we investigated the effects of TN-C on LV remodeling and the biological function of TN-C during the acute phase of inflammatory responses after myocardial infarction.
The 8 to 10 weeks old male wild type (WT) and TN-C knock-out (KO) mice were divided into 4 groups of WT+Sham, KO+Sham, WT+MI and KO+MI. Mice 12 weeks post-MI, the survival rate of both WT+MI (48.3%,14 of 29 mice) and KO+MI (55.6%,15 of 27 mice) groups had no significant difference. However, TN-C KO group had the better cardiac function than WT had (LVEF, 19.02±6.31% vs 10.63±4.43%; p<0.001). Interstitial fibrosis at border area was significantly increased in the WT +MI group to compare with that of KO+MI, whereas the extent of fibrosis in the remote area revealed no significant difference between the two groups. By RT-PCR analysis, WT+MI group showed significantly higher expression of atrial natriuretic peptide at the border including infarcted areas than that of KO+MI at chronic MI phase. At acute phase, fluorescence activated cell sorting analysis showed that ratio of CD45+, CD11b+, Ly6c high pro-inflammatory monocyte were significantly decreased, whereas CD45+, F4/80+, CD206+, anti-inflammatory M2 macrophage were significantly increased in KO+MI compared with WT+MI group 7 days after MI. RT-PCR analysis showed that the expression of IL-10, an anti-inflammatory cytokine, was significantly higher in KO+MI than WT+MI.
These findings suggest, TN-C aggravates the deterioration of LV function due to MI partly by modulating inflammation at acute phase.
Author Disclosures: T. Kimura: None. A. Sato: None. K. Tajiri: None. W. Zeng: None. S. Sakai: None. T. Yoshida: None. M. Hiroe: None. K.I. Yoshida: None. K. Aonuma: None.
- © 2014 by American Heart Association, Inc.