Expression of matrix metalloproteinase activity in idiopathic dilated cardiomyopathy: a marker of cardiac dilatation.
BACKGROUND
Idiopathic dilated cardiomyopathy (DCM), ventricular systolic dysfunction and chamber dilatation are accompanied by architectural remodeling, wall thinning and cardiac myocyte slippage. Recent work has demonstrated an association between collagen degradation and an increased expression of matrix metalloproteinases (MMPs). Accordingly, we have sought to correlate (a) collagen degradation with MMP elevations and, (b) assay the neutralizing potential of a known inhibitor of MMP, tetracycline on MMPs in DCM.


METHODS
Assessment of LV volume and shape by 2-D echocardiography was performed. Light microscopic assessment of histopathology in picrosirius red stained biopsy samples of 11 DCM patients and six post-transplant patients was performed. Zymographic estimation of MMP activity and influence of tetracycline on MMP activity was assessed.


RESULTS
Small amount of interstitial collagen was noted in the control group, whereas in the DCM hearts, chamber dilatation was associated with areas of scanty myocyte necrosis, islands of excess collagen, and focal areas of absent or scanty collagen with intact myocytes. In cardiomyopathic tissue, collagenase activity was markedly elevated at 63% compared with 8% in post-transplant tissue. Tetracycline at a concentration of 285+/-10 microM (IC50) inhibited collagenase activity by 50% in cardiomyopathic tissue.


CONCLUSIONS
Areas of focal interstitial collagen accumulation were accompanied by collagen fiber lysis and increased collagenase activity in dilated cardiomyopathy. This enhanced collagenolytic activity found in endomyocardial biopsy tissue was inhibited by tetracycline. The non-antibiotic property of tetracycline may be of potential value in the prevention of ventricular dilatation in idiopathic dilated cardiomyopathy.
Reddy
Hanumanth K
HK
Division of Cardiology, Department of Internal Medicine, University of Missouri-Columbia, MO, USA.
Tjahja
Imam E
IE
Campbell
Scott E
SE
Janicki
Joseph S
JS
Hayden
Melvin R
MR
Tyagi
Suresh C
SC
D000328:Adult; D015415:Biomarkers; D002311:Cardiomyopathy, Dilated / Q000201:enzymology*; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004452:Echocardiography / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005355:Fibrosis; D006331:Heart Diseases / Q000628:therapy; D016027:Heart Transplantation; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D009336:Necrosis; D013752:Tetracycline / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D015415:Biomarkers; D003094:Collagen; D017364:Collagenases; D020782:Matrix Metalloproteinases; D013752:Tetracycline