Tenascin-C Modulates Adhesion of Cardiomyocytes to Extracellular Matrix during Tissue Remodeling after Myocardial Infarction

Abstract

SUMMARY: Tenascin-C (TNC), an extracellular matrix glycoprotein, plays important roles in tissue remodeling. TNC is not normally expressed in adults but reappears under pathologic conditions. The present study was designed to clarify the contribution of TNC to ventricular remodeling after myocardial infarction. We examined the expression of TNC after experimental myocardial infarction in the rat by immunohistochemistry and in situ hybridization. Within 24 hours of permanent coronary ligation, interstitial fibroblasts in the border zone started to express TNC mRNA. The expression of TNC was down-regulated on Day 7 and was no longer apparent by Day 14 after infarction. During the healing process, TNC protein and TNC-producing cells were found at the edges of the residual myocardium. Some of the TNC-producing cells were immunoreactive for ␣-smooth muscle actin. In culture, TNC increased the number of cardiomyocytes attached to laminin but inhibited the formation of focal contacts at costameres. The results indicate that during the acute phase after myocardial infarction, interstitial cells in the border zone synthesize TNC, which may loosen the strong adhesion of surviving cardiomyocytes to connective tissue and thereby facilitate tissue reorganization. (Lab Invest 2001, 81:1015-1024.T enascins constitute a family of extracellular matrix glycoproteins (Erickson, 1993). The first member found, tenascin-C (TNC), is highly expressed in embryonic tissue during morphogenesis and sparsely expressed in the adult, but reappears during wound healing, regeneration, or cancer invasion (Chiquet-Ehrismann et al, 1986). TNC is transiently expressed in distinct areas in association with active tissue remodeling. Various in vitro findings have indicated that TNC has multiple functions in the regulation of cell migration, proliferation, and apoptosis (Chung et al, 1996;Jones and Jones, 2000). TNC counterbalances cell adhesion to substrata, correlated with cytokinesis and motility, and prevents cells from adhering too tightly to other extracellular matrix proteins (Chiquet-Ehrismann, 1995;Chiquet-Ehrismann et al, 1988;Chung et al, 1996;Murphy-Ullrich et al, 1991;Prieto et al, 1992).In the heart, TNC appears only at very early stages of embryonic development and may play important roles in the differentiation of cardiomyocytes, structural organization of the myocardium, or development of coronary vessels . TNC is not normally expressed in the adult heart but reappears under various pathologic conditions such as dilated cardiomyopathy, myocarditis, or myocardial infarction (Imanaka-Yoshida et al, 1998, 2000Tamura et al, 1996;Willems et al, 1996).To understand its roles in tissue remodeling in the diseased myocardium, we examined the expression of TNC during tissue repair after experimental myocardial infarction in rats. Sequential changes in the localization of the molecule were analyzed by immunohistochemistry, and TNC-producing cells were identified by in situ hybridization (ISH) combined with immunohistochemistry. Additionally, to ...

Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs)

“…Tenascin-C TN-C is a large hexameric matricellular glycoprotein that is normally expressed at low levels in the adult heart but is markedly upregulated in response to myocardial damage [117,118]. TN-C is a ligand for several integrin receptors [119], as well as for TLR4 [120].…”

“…In synovial fibroblasts, TN-C has been shown to couple to proinflammatory cytokine expression via TLR4 activation [120]. TN-C is produced by a wide variety of cardiovascular cell types [118], including CF [94,117]. TN-C expression is an independent predictor of mortality in patients with dilated cardiomyopathy [121] and serum TN-C levels are a potentially useful predictor of LV remodelling and prognosis after MI [122].…”

The Recent Advances in the Serological Detection of Acute Myocardial Infarction

“…In animal models of MI, tenascin-C expression can be detected in the infarct border zone, and is thought to loosen the strong adhesion of surviving cardiomyocytes to connective tissue [51]. Accordingly, tenascin-C aggravates left ventricle remodeling and dysfunction after MI in mice; its deletion attenuates adverse left ventricle fibrosis and dysfunction, without affecting infarct sizes or survival rates [52].…”

The Relationship between Tenascin-C Levels and the Complexity of Coronary Lesion after Myocardial Infarction

“…It also has multiple functions, such as cell proliferation 3) , migration 4) , differentiation 5) and apoptosis 6) . Tenascin-C is also expressed in various pathological conditions, including human coronary atherosclerotic plaque 7) , abdominal aorta aneurysm 8) , MI 2,9) , myocarditis 10) , malignant tumours [11][12][13][14] and pulmonary hypertension 15,16) . Tenascin-C levels increase after cardiac injury and inflammation.…”

“…Tenascin-C is an extracellular matrix glycoprotein that reorganizes the cell shape of the heart during cardiac repair after acute MI 2) . It also has multiple functions, such as cell proliferation 3) , migration 4) , differentiation 5) and apoptosis 6) .…”