Tenascin and Fibronectin Expression in Healing Human Myocardial Scars

Abstract

Fibronectin and tenascin are matrix proteins known to be present in early experimental wound healing. As only limited data are available regarding early matrix changes in human myocardial infarction, the presence of tenascin and fibronectin was studied in human myocardial infarctions of different post‐infarction times (6 h to 17 years), using immunohistochemistry. In normal myocardium, fibronectin immunostaining was found in the subendothelial space in vessels. Tenascin was not present in normal myocardium. While fibronectin was demonstrated in the ischaemic cardiomyocytes within 1 day, tenascin was found 4–6 days post‐infarction and was located at the margin of the area of infarction. Tenascin expression then shifted from the margin to the centre of the area of infarction, where it could be found 2–3 weeks post‐infarction. More than 4 weeks post‐infarction, the scar tissue consisted of collagen fibres, with sparse (myo)fibroblasts. By that time, both tenascin and fibronectin expression had disappeared. Another interesting observation in this study was the presence of tenascin, but not fibronectin, surrounding vacuolated glycogen‐rich cells, or so‐called hibernating cardiomyocytes.

Matricellular proteins in the heart: possible role during stress and remodeling

“…However, TN-C reappeared under pathological conditions, including myocarditis [22], myocardial infarction [12,23], hibernating myocardium [24], and during dilated cardiomyopathy [25]. Its expression correlated with cardiac injury and inflammation, and level of TN-C expression has been proposed as a marker for the severity of viral myocarditis [22].…”

Changes in extra cellular matrix remodelling and re-expression of fibronectin and tenascin-C splicing variants in human myocardial tissue of the right atrial auricle: implications for a targeted therapy of cardiovascular diseases using human SIP format antibodies

“…Among the large number of ECM molecules involved in cardiac remodelling, the cell adhesion modulating molecules fibronectin and tenascin-C are of functional importance for cell-cell and cell-matrix interactions as well as the regulation of cell growth, adhesion, migration and proliferation during heart development and wound healing (Farhadian et al 1995;Imanaka-Yoshida et al 2003;Imanaka-Yoshida et al 2004;Kim et al 1999;Pelouch et al 1993;Willems et al 1996). Different oncofetal variants of fibronectin and tenascin-C are generated by alternative splicing or by posttranslational modifications leading to ED-A, ED-B and III-CS domain containing fibronectin or A1, C and D domain containing tenascin-C (Borsi et al 1995;Schwarzbauer 1991).…”

“…Different oncofetal variants of fibronectin and tenascin-C are generated by alternative splicing or by posttranslational modifications leading to ED-A, ED-B and III-CS domain containing fibronectin or A1, C and D domain containing tenascin-C (Borsi et al 1995;Schwarzbauer 1991). These variants are mostly absent in healthy myocardial tissue and are reexpressed during pathological conditions such as acute myocardial infarction, myocardial injury or dilated cardiomyopathy (Aso et al 2004;Gabler et al 1996;ImanakaYoshida et al 2002;Morimoto et al 2005;Tersasaki et al 2007;Willems et al 1996). Analysis of differential re-expression of fibronectin and tenascin-C splicing variants is of high clinical interest since recombinant human antibodies against ED-A (ED-A ?…”

Extra cellular matrix remodelling after heterotopic rat heart transplantation: gene expression profiling and involvement of ED-A+ fibronectin, alpha-smooth muscle actin and B+ tenascin-C in chronic cardiac allograft rejection

“…In particular, Wbronectin and tenascin-C could be shown to crucially participate in the regulation of cell-cell and cell-matrix interactions during heart development and in diVerent cardiac diseases (Farhadian et al 1995;Willems et al 1996;Kim et al 1999;Imanaka-Yoshida et al 2003Astrof and Hynes 2009;Pawitan 2010). Both proteins occur as diVerent molecular variants generated by alternative splicing or post-translational modiWcations.…”