Diagnostic utility of tenascin-C for evaluation of the activity of human acute myocarditis

Abstract

Tenascin-C (TN-C) is an extracellular matrix protein that is expressed transiently in close association with tissue remodelling in various body sites. In the heart, TN-C is only present during early stages of development, is not expressed in the normal adult, but reappears in pathological states. The purpose of this study was to analyse the expression of TN-C in myocardial tissue from myocarditis patients, and to evaluate the diagnostic value of immunostaining for TN-C in the assessment of inflammatory activity in biopsy specimens. A total of 113 biopsy specimens obtained from 32 patients with a clinical diagnosis of acute myocarditis were examined by immunohistochemistry and in situ hybridization for TN-C. The immunostaining was semi-quantified and compared with histological diagnosis according to the Dallas criteria. Furthermore, serial biopsies from 22 patients were taken during convalescence, and sequential changes in TN-C levels were analysed. Expression of TN-C was specifically detected in endomyocardial biopsy specimens from patients with active-stage inflammation, and disappeared in healed stages. The degree of expression of TN-C correlated with the severity of histological lesions. These data suggest that TN-C reflects disease activity in cases of human myocarditis. Immunostaining for TN-C could enhance the sensitivity and accuracy of diagnosis using biopsy specimens.

Higher Serum Tenascin-C Levels Reflect the Severity of Heart Failure, Left Ventricular Dysfunction and Remodeling in Patients With Dilated Cardiomyopathy

“…As previously reported, TN-C is specifically expressed in the myocardial inflammatory lesions of myocarditis [16][17][18] and AMI. 12,15 Furthermore, serum TN-C levels are elevated in AMI patients, reflecting local expression of TN-C in the infarcted myocardium.…”

“…In the pathological myocardium, results obtained from experimental animal models, as well as human myocarditis samples, have identified that the major source of TN-C is interstitial fibroblasts. 12,16,18 Various cytokines, growth factors, hypoxia, mechanical stress, acidosis, and angiotensin II, which are important mediators of myocardial injury and inflammation during progression of heart failure in DCM, stimulate cardiac fibroblasts to synthesize TNC in vitro. 28 In addition, endothelial cells and vascular smooth muscle cells of various organs have the potential to synthesize TN-C under these same stimulations.…”

Fulminant Myocarditis With Prolonged Active Lymphocytic Infiltration After Hemodynamic Recovery

“…An endomyocardial biopsy (EMB) from the right ventricular septum was performed, and the biopsy specimens showed massive lymphocytic infiltration associated with myocytolysis without obvious myocardial fibrosis ( Figure 1B and C). Strong immunostaining for tenascin-C, a marker of active inflammation, 3) was seen around cardiomyocytes ( Figure 1D). His troponin-I level was 31.3 ng/mL.…”

Tenascin-C in Cardiovascular Tissue Remodeling

“…Immunostaining for TN-C significantly improves the sensitivity of a histological diagnosis of myocarditis. 38 The serum level of TN-C measured by enzyme-linked immunosorbent assay may reflect its local expression in the myocardium. For example, serum TN-C in patients with acute MI is significantly elevated, peaks at day 5, and then gradually decreases.…”