[Involvement of matrix metalloproteinases in the regulation of myocardial extracellular matrix in patients with congestive heart failure].
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.


CONCLUSIONS
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.
Yang
Yong-jian
YJ
Department of Cardiology, General Hospital of Chengdu Military Command, Chengdu 610083, China.
Zhang
Xin
X
Zhu
Wen-ling
WL
Huang
Yan
Y
D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis; D005455:Fluorescent Antibody Technique; D006333:Heart Failure / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000097:blood; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000097:blood; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D019063:Tenascin / Q000096:biosynthesis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000097:blood; D020257:Ventricular Remodeling
D005353:Fibronectins; D019063:Tenascin; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9