OBJECTIVE

To investigate the expression of the matrix metalloproteinases (MMP)-2, -3, and 9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), fibronectin (FN), and tenascin-C (TN-C) in the myocardium, and their relationship with the myocardial remodeling and heart function in the patients with congestive heart failure (CHF).

METHODS

A few tissues of papillary muscles of left ventricle were taken from 39 patients with mitral insufficiency during mitral valve replacement, and from 8 organ donors who had died of accidents to undergo pathological examination and to detect the protein expression of MMP-2, -3, and 9, and TIMP-1 by immunoprecipitation and the expression of FN and TN-C by immunofluorescence test. Peripheral blood samples were collected from these 39 patients and 30 normal controls to examine the plasma MMPs and TIMP-1 by ELISA.

RESULTS

Typical myocardial remodeling was seen in the myocardial tissues of the CHF patients. The plasma levels of MMP-2, -3, and -9 of the CHF patients in the cardiac function classes II - IV were all significantly higher than those of the normal controls (P < 0.05 or P < 0.01) with a tendency to increase with the deterioration of heart function, The plasma level of TIMP-1 of the CHF patients in the cardiac function classes II - IV were all significantly higher than that of the normal controls (P < 0.05 or P < 0.01) with a tendency to decrease with the deterioration of heart function. The protein expression levels of MMP-2, -3, and -9 in the myocardium of the CHF patients in the cardiac function classes III - IV were all significantly higher than those of the normal controls (P < 0.05 or P < 0.01) with a tendency to increase with the deterioration of heart function. The protein expression levels of TIMP-1 in the myocardium of the CHF patients in the cardiac function classes III - IV were all significantly lower than that of the normal controls (P < 0.05 or P < 0.01) with a tendency to decrease with the deterioration of heart function. The protein expression levels of FN in the myocardium of the CHF patients in the cardiac function classes II - IV were all significantly lower than that of the normal controls (all P < 0.05) with a tendency to decrease with the deterioration of heart function. The protein expression levels of TN-C in the myocardium of the CHF patients in the cardiac function classes II - IV were all significantly higher than that of the normal controls (all P < 0.01) with a tendency to increase with the deterioration of heart function.

CONCLUSION

The increasing expression of MMP-2, -3, and -9 and the decreasing expression of TIMP-1 contribute to the myocardial remodeling, thus changing the extracellular matrix in the myocardium tissue and leading to the development and progression of CHF.