Dilated cardiomyopathy is associated with an increase in the type I/type III collagen ratio: a quantitative assessment

Abstract

Objectives: The aim of this study was to quantify total collagen and the type I/type III collagen ratio and their localization in hearts with dilated cardiomyopathy.

Background: Patients with dilated cardiomyopathy have an increase in intramyocardial fibrillar collagen. Types I and III are the main constituents and have different physical properties that may affect cardiac compliance.

Methods: Nineteen hearts with dilated cardiomyopathy were studied (17 cardiac explants, 2 hearts obtained at autopsy) and compared with reference hearts. Total collagen was determined by hydroxyproline analysis. Collagen types I and III were analyzed using the cyanogen bromide method and immunohistochemical analysis followed by microdensitophotometric quantification. Localization of collagen types I and III was established at the light and electron microscopic levels. Immunoelectron microscopy provided information regarding their localization.

Results: Total collagen and the collagen type I/type III ratio were increased in hearts with dilated cardiomyopathy (p < 0.05). Electron microscopy showed a diffuse increase in collagen fibrils in the endomysium; the perimysium showed an inhomogeneous increase. Collagen fibrils were thicker, and fibrous long-spacing collagen occurred in the endomysium. Immunoelectron microscopic findings confirmed an increase in type I collagen.

Conclusions: Hearts with dilated cardiomyopathy have a statistically significant increase in the collagen type I/type III ratio. The changes occur in the endomysium and perimysium, although with differences in distribution. These changes in intramyocardial collagen may be clinically relevant because they may affect cardiac rigidity and, therefore, eventually may render the heart less compliant. Further studies are needed to evaluate at what point in the course of the disease these changes appear.