Abstract: 844-2 |
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Circulating
Tumor Necrosis Factor-Alpha and Matrix Metalloproteinase Activities
in Patients With Idiopathic Dilated Cardiomyopathy: Effects
of Beta-Blocker on Cardiac Matrix Remodeling Topic: Cardiomyopathies/Myocarditis/Pericardial Disease Background: Matrix metalloproteinases (MMPs) contribute to myocardial matrix degradation during the remodeling process in the failing heart. Recently, increased myocardial MMP activity has been reported to occur in clinical forms of dilated cardiomyopathy. Tumor necrosis factor (TNF)-alpha is an important regulator of MMP gene expression. This study was designed to clarify the relationship between circulating TNF-alpha and MMP activities in patients with idiopathic dilated cardiomyopathy (IDC) and to evaluate the effect of beta-blocker on circulating MMP activity in IDC. Methods: We studied 34 patients with IDC and 10 healthy control subjects. Serum levels of TNF-alpha, MMP-1, MMP-3 and MMP-9 were measured using enzyme-linked immunosorbent assay. Plasma levels of norepinephrine and brain natriuretic peptide (BNP) were also measured. In 20 patients who had been treated with angiotensin II type 1 receptor blockers, carvedilol was administered in addition to the combination therapy. Results: Serum levels of TNF-alpha, MMP-1, MMP-3 and MMP-9 were significantly higher in all patients with IDC than in control subjects (p< 0.05 for all). There was a significant positive correlation between TNF-alpha and MMP-9 levels (r= 0.764, p= 0.01). The MMP-9 levels were also positively correlated with norepinephrine levels (r= 0.750, p= 0.005). In addition, there was a positive correlation between MMP-1 and BNP levels (r= 0.647, p= 0.022). In patients treated with carvedilol, the high levels of MMP-1, MMP-9 and TNF-alpha were significantly decreased during the treatment (p< 0.05 for all), although MMP-3 levels remained unchanged. Conclusions:Circulating TNF-alpha is closely related to MMP activity in IDC patients, and carvedilol can modulate circulating MMP activity as well as TNF-alpha activity. The inhibition of TNF-alpha activity may directly influence cardiac matrix remodeling in IDC.
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