Does dilated cardiomyopathy (EF <50%) alter the myocardial collagen type I/type III ratio compared to mild left ventricular dysfunction (EF >50%)?
Dilated cardiomyopathy is associated with a differential increase in collagen type I and III, leading to an increased Col I/Col III ratio which may contribute to myocardial stiffness and dysfunction.
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=18) were examined. Col I, Col III, and transforming growth factors-beta1 (TGF-beta1) and -beta2 (TGF-beta2) 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%. The Col III mRNA abundance showed a 2.0-fold increase (P50% (Col I/Col III, 6. 4). In addition, total collagen content was increased in 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-beta1 and TGF-beta2 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.
Pauschinger et al. (Tue,) studied this question.