Dilated cardiomyopathy is associated with significant changes in collagen type I/III ratio

Background-It is controversial whether myocardial fibrosis in end-stage dil ated cardiomyopathy (DCM) is associated with altered collagen type I/type I II (Col I/Col III) ratio. Methods and Results-Patients with DCM (ejection fraction [EF] <50%, n=12) a nd with mild global left ventricular dysfunction (EF >50%, n=18) were exami ned. Col I, Col III, and transforming growth factors-beta(1) (TGF-beta(1)) and -beta(2) (TGF-beta(2))gene expression in endomyocardial biopsies was ev aluated by quantitative competitive reverse transcriptase-polymerase chain reaction (qRT-PCR). Collagen content was quantified after picrosirius red a nd immunohistological staining and by hydroxyproline assay. In patients wit h 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 pro tein level versus that found in patients with EF >50%. The Col III mRNA abu ndance showed a 2.0-fold increase (P<0.04). There was a relevant shift in t he 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 coll agen content was increased in patients with EF <50% (n=3) (4.3 +/- 0.1%) co mpared with patients with EF >50% (n=8) (2.7 +/- 0.9%) (P<0.004). The bioch emically determined ratio of hydroxyproline/total protein (n=12) was correl ated to the Col I mRNA abundance (P<0.05, r=0.77). TGF-beta(1) and TGF-beta (2) showed elevated myocardial mRNA abundances (1- to 7-fold and 4- to 5-fo ld, respectively) in DCM patients. Conclusions-Differential increase of Col I and Col III leads to an increase d Col I/Col III ratio in DCM myocardium. Because Col I provides substantial tensile strength and stiffness, this may contribute to systolic and in par ticular diastolic dysfunction in DCM.