Objective: The cytokine tumor necrosis factor (TNF) alpha has been causally linked to left ventricular (LV) remodeling, but the molecular basis for this effect is unknown. It is essential to study the changes of plasma levels of TNF alpha and matrix metalloproteinase-2,3,9 (MMP-2,3,9) expressions in myocardium during congestive heart failure (CHF).
Methods: Plasma levels of TNF alpha were measured with enzyme-linked immunoassay in CHF patients of various degrees and in healthy controls. Using Western blotting assay, we detected the protein expressions of MMP-2,3,9 on myocardial tissue in CHF patients and in healthy controls. Cardiac function parameters were measured with echocardiographic studies.
Results: Plasma levels of TNF alpha increased significantly in patients with CHF (P < 0.05 or < 0.01). The protein expressions of MMP-2,3,9 were significantly higher in patients with CHF than in controls (P < 0.05 or < 0.01). The higher the degree of CHF, the greater the numbers of expressions. No changes of MMP-2 could be found between the controls and CHF patients of NYHA II. There was a positive correlation between plasma levels of TNF alpha and the protein expressions of MMP-2,3,9 (P < 0.01 or < 0.001).
Conclusions: It is suggested that alterations of TNF alpha may stimulate the expressions of MMPs, contribute to myocardial remodeling and lead to the development and progression of congestive heart failure. These changes may induce a direct effect on the progression and deterioration of heart failure.