Elevated serum markers of collagen degradation in patients with mild to moderate dilated cardiomyopathy.
OBJECTIVE
Left ventricular (LV) dilation and myocardial remodelling are hallmarks of heart failure in idiopathic dilated cardiomyopathy (DCM). Interstitial collagen is essential for LV integrity and function while degradation of collagen by collagenases, especially matrix-metalloproteinases (MMPs), are suggested to contribute to ventricular dilation. In the present study, serological markers of collagen metabolism were investigated.


RESULTS
Serum levels of MMP-1 and its inhibitor (TIMP-1), the markers for collagen degradation type I (collagen carboxyterminal telopeptide (ICTP)) and synthesis (carboxyterminal propeptide of type I procollagen (PICP)) were quantified by ELISA and RIA of 43 patients with DCM and 47 age-matched control subjects. Free MMP-1 serum concentration was significantly increased in the DCM group (5.29+/-0.83 vs. 2.22+/-0.29 ng/ml; P=0.01) as well as the free TIMP-1 concentration (206.54+/-12.65 vs. 181.44+/-8.55 ng/ml; P=0.05). The free MMP-1/TIMP-1-ratio was higher in DCM than in the control group (0.030+/-0.005 vs. 0.012+/-0.001; P=0.01). ICTP was significantly increased (7.60+/-1.21 vs. 3.44+/-0.19 microg/l; P<0.001). PICP was not significantly increased (125.29+/-8.93 microg/l vs. 113.11+/-5.47 microg/l; P=n.s.). Free MMP-1 and MMP-1/TIMP-1-ratio correlated with LV end diastolic diameter [cm/m(2) body surface area (BSA)] (r=0.28; P=0.03 and r=0.34; P=0.01, respectively) as well as with cardiac index (CI) (r=-0.32; P=0.04 and r=-0.33; P=0.04, respectively) in patients with DCM.


CONCLUSIONS
Serum markers of collagen degradation are elevated and might be valuable markers for progression of LV dilation in patients with DCM.
Schwartzkopff
Bodo
B
Department of Cardiology, Angiology and Pneumology, Heinrich-Heine University Düsseldorf, Moorenstrasse 5, Germany. schwartzkopff@med.uni-duesseldorf.de
Fassbach
Michael
M
Pelzer
Beate
B
Brehm
Michael
M
Strauer
Bodo E
BE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000201:enzymology; D003094:Collagen / Q000097:blood*; D017364:Collagenases / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000201:enzymology; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000201:enzymology; D020257:Ventricular Remodeling / Q000502:physiology
D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D017364:Collagenases; D020782:Matrix Metalloproteinases; D020781:Matrix Metalloproteinase 1