Abstract 1613: Enhanced Expression of Tenascin-C in Granulomas of Patients With Active Cardiac Sarcoidosis
Introduction: Tenascin-C (TN-C) is a member of the matricellular proteins that do not subserve a primary structural role, but function rather as modulators of cell-matrix interactions, with being evident at sites of inflammation, tissue remodeling or wound healing. Although TN-C is likely involved in the inflammatory process in the granulomatous tissue, their in situ expression in the sarcoid heart has not been clarified.
Hypothesis: We assessed the hypothesis that serum levels of TN-C are increased in patients with sarcoidosis, and the expression of TN-C is upregulated in the myocardium of patients with active cardiac sarcoidosis.
Methods: Serum TN-C levels were measured in 40 patients with sarcoidosis and 23 patients with idiopathic dilated cardiomyopathy (DCM). Sera from 20 normal volunteers served as controls. In addition, we immunohistochemically examined the expression profiles of TN-C in the myocardium from 12 patients with active cardiac sarcoidosis and 10 DCM patients.
Results: Serum TN-C levels were significantly higher in patients with sarcoidosis than in normal controls [79.7±43.3 (SD) ng/ml vs. 30.9±8.8 ng/ml, p=0.001]. In the sarcoidosis group, serum TN-C levels in patients with definite cardiac involvement (n=10) were significantly higher than in those without it (n=30) (119.6±45.0 ng/ml vs. 66.4±34.0 ng/ml, p=0.005) and they were also higher than in DCM patients (vs. 68.2±24.3 ng/ml, p=0.006). Immunohistochemically, expression of TN-C was markedly enhanced in the extracellular matrix surrounding multinucleated giant cells and macrophages in the sarcoid granulomas. TN-C expression was limited to areas with well-formed, active granulomas.
Conclusions: TN-C, produced in extracellular matrix, may be involved in the pathogenesis of sarcoid granulomas. The measurement of serum TN-C levels is useful for the diagnosis of sarcoidosis, and their higher levels may suggest the cardiac involvement.