Tenascin-C Enhances Inflammaoty Response during the 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.

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Tenascin-C may aggravate left ventricular remodeling and function after myocardial infarction in mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00255.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. H1072-H1078 ◽

Cited By ~ 81

Author(s):

Tomohiro Nishioka ◽

Katsuya Onishi ◽

Naoshi Shimojo ◽

Yuka Nagano ◽

Hidenori Matsusaka ◽

...

Keyword(s):

Myocardial Infarction ◽

Ventricular Remodeling ◽

Diastolic Pressure ◽

Interstitial Fibrosis ◽

Left Ventricular Remodeling ◽

Left Ventricular ◽

High Serum ◽

Border Zone ◽

Myocardial Stiffness ◽

Tenascin C

Tenascin-C (TN-C) is an extracellular matrix glycoprotein with high bioactivity. It is expressed at low levels in normal adult heart, but upregulated under pathological conditions, such as myocardial infarction (MI). Recently, we (Ref. 34 ) reported that MI patients with high serum levels of TN-C have a greater incidence of maladaptive cardiac remodeling and a worse prognosis. We hypothesized that TN-C may aggravate left ventricular remodeling. To examine the effects of TN-C, MI was induced by ligating coronary arteries of TN-C knockout (KO) mice under anesthesia and comparing them with sibling wild-type (WT) mice. In WT+MI mice, TN-C expression was upregulated at day 1, peaked at day 5, downregulated and disappeared by day 28, and the molecule was localized in the border zone between intact myocardium and infarct lesions. The morphometrically determined infarct size and survival rate on day 28 were comparable between the WT+MI and KO+MI groups. Echocardiography and hemodynamic analyses demonstrated left ventricular end-diastolic diameter, myocardial stiffness, and left ventricular end-diastolic pressure to be significantly increased in both WT+MI and KO+MI mice compared with sham-operated mice. However, end-diastolic pressure and dimension and myocardial stiffness of KO+MI were lower than those of the WT+MI mice. Histological examination revealed normal tissue healing, but interstitial fibrosis in the residual myocardium in peri-infarcted areas was significantly less pronounced in KO+MI mice than in WT+MI mice. TN-C may thus accelerate adverse ventricular remodeling, cardiac failure, and fibrosis in the residual myocardium after MI.

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A novel biomarker, Tenascin C, for predicting left ventricular remodeling in acute myocardial infarction

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2008.07.036 ◽

2008 ◽

Vol 14 (7) ◽

pp. S137

Author(s):

Akira Sato ◽

Yoshihiro Seo ◽

Satoru Kawano ◽

Kazutaka Aonuma ◽

Michiaki Hiroe

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Left Ventricular ◽

Tenascin C

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Tongxinluo Improves Cardiac Function and Ameliorates Ventricular Remodeling in Mice Model of Myocardial Infarction through Enhancing Angiogenesis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/813247 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Wen-Wu Bai ◽

Yi-Fan Xing ◽

Bo Wang ◽

Xiao-Ting Lu ◽

Ying-Bin Wang ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Cardiac Remodeling ◽

Ventricular Remodeling ◽

Interstitial Fibrosis ◽

Binding Activity ◽

Control Group ◽

High Dose ◽

Mice Model ◽

Male Adult

Background. Myocardial infarction (MI) is a major cause of morbidity and mortality in the world. Tongxinluo (TXL) is a traditional Chinese compound prescription which has cardioprotective functions. The present study was aimed to determine the effect of TXL on postischemic cardiac dysfunction and cardiac remodeling and to elucidate the underlying mechanisms.Methods and Results. MI was performed by ligation of left anterior descending coronary artery (LAD) in male adult mice. Mice were randomly divided into four groups: (1) sham group (Sham); (2) MI-control group (Control); (3) MI-low dose TXL group (TXL-L); and (4) MI-high dose TXL (TXL-H) group. Compared with the control group, TXL treatment restored cardiac function, increased revascularization, attenuated cardiomyocyte apoptosis, and reduced interstitial fibrosis. TXL treatment increased the phosphorylation of Akt, extracellular signal regulated kinase (ERK), and endothelial nitric oxide synthase (eNOS); the expression of phosphatidylinositol3-kinase (PI3K), hypoxia-inducible factors 1α(HIF-1α), and vascular endothelial growth factor (VEGF); and the DNA binding activity of HIF-1αafter MI.Conclusion. TXL may improve cardiac function and ameliorate cardiac remodeling by increasing neovascularization through enhancing the phosphorylation of Akt and ERK, the expression and activity of HIF-1α, and the protein level of VEGF and p-eNOS.

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