(Circulation. 1999;99:2750-2756.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Dilated Cardiomyopathy Is Associated With Significant Changes in Collagen Type I/III ratio
From the Medical Clinic II, University Hospital Benjamin Franklin, Freie Universität Berlin, Germany.
Correspondence to Matthias Pauschinger, MD, Medical Clinic II, University Hospital Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany.
Background—It is controversial whether myocardial fibrosis in end-stage dilated cardiomyopathy (DCM) is associated with altered collagen type I/type III (Col I/Col III) ratio.
Methods and Results—Patients with DCM (ejection fraction [EF] <50%, n=12) and with mild global left ventricular dysfunction (EF >50%, n=18) were examined. Col I, Col III, and transforming growth factors-ß1 (TGF-ß1) and -ß2 (TGF-ß2) gene expression in endomyocardial biopsies was evaluated by quantitative competitive reverse transcriptase–polymerase chain reaction (qRT-PCR). Collagen content was quantified after picrosirius red and immunohistological staining and by hydroxyproline assay. In patients with EF <50%, there was a pronounced 2- to 6-fold increase of myocardial Col I mRNA abundance (P<0.01), with a corresponding 1.6-fold increase at the protein level versus that found in patients with EF >50%. The Col III mRNA abundance showed a 2.0-fold increase (P<0.04). There was a relevant shift in the Col I/Col III mRNA ratio for DCM patients (Col I/Col III, 8.2) compared with patients with an EF >50% (Col I/Col III, 6.4). In addition, total collagen content was increased in patients with EF <50% (n=3) (4.3±0.1%) compared with patients with EF >50% (n=8) (2.7±0.9%) (P<0.004). The biochemically determined ratio of hydroxyproline/total protein (n=12) was correlated to the Col I mRNA abundance (P<0.05, r=0.77). TGF-ß1 and TGF-ß2 showed elevated myocardial mRNA abundances (1- to 7-fold and 4- to 5-fold, respectively) in DCM patients.
Conclusions—Differential increase of Col I and Col III leads to an increased Col I/Col III ratio in DCM myocardium. Because Col I provides substantial tensile strength and stiffness, this may contribute to systolic and in particular diastolic dysfunction in DCM.
Key Words: cardiomyopathy • collagen • growth substances • remodeling • polymerase chain reaction
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