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Collagen in dilated cardiomyopathy--scanning electron microscopic and immunohistochemical observations
14th Department of Internal Medicine, Shimane Medical University, Izumo, Japan.
Insights
Dilated cardiomyopathy (DCM) alters heart collagen structure, with increased type I and III collagen in the endomysium and perimysium. Giant coiled fibers were observed in DCM hearts, offering insights into cardiac pathology.
Area of Science:
- Cardiovascular Pathology
- Biochemistry
- Electron Microscopy
Background:
- Dilated cardiomyopathy (DCM) is a severe heart condition characterized by cardiac dysfunction.
- Collagen remodeling plays a critical role in the pathogenesis of heart diseases.
- Understanding collagen changes in DCM is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the ultrastructural characteristics and localization of collagen types I-VI in human hearts affected by dilated cardiomyopathy.
- To compare collagen architecture in DCM hearts with healthy controls.
- To elucidate the role of specific collagen types in the cardiac lesions of DCM.
Main Methods:
- Scanning electron microscopy (SEM) using cell-maceration for collagen fiber architecture.
- Immunohistochemistry with monoclonal antibodies for localizing collagen types I-VI.
- Analysis of formalin-fixed human heart tissues from DCM patients and healthy controls.
Main Results:
- In DCM, a dense endomysial network of fine fibrils rich in collagen types I and III was observed.
- Perimysial collagen bundles and strands increased in number and thickness, featuring giant coiled fibers (20-30 microns).
- Type V collagen increased in the intracellular matrix of DCM myocardium; type II collagen was absent.
Conclusions:
- Formalin fixation does not significantly alter collagen ultrastructure or immunoreactivity.
- Significant alterations in collagen composition and organization, particularly increased type I and III collagen, characterize DCM.
- The observed collagen changes, including giant coiled fibers, provide key insights into DCM pathogenesis and cardiac remodeling.
Abstract:
The ultrastructural characteristics of collagen and the localization of collagen types were studied in formalin-fixed autopsied human hearts from patients who died in an advanced stage of dilated cardiomyopathy (DCM). The three-dimensional architecture of collagen fibers was studied by scanning electron microscopy by using the cell-maceration method. The localization of collagen type I-VI was demonstrated immunohistochemically using monoclonal antibodies specific to each collagen following the treatment of specimens with trypsin. In the hearts obtained from control subjects without heart disease, there were no significant differences in the ultrastructure and localization of collagens between the fresh and the formalin-fixed hearts. Therefore, formalin-fixation did not affect the ultrastructure of collagen or the immunoreactivity. In DCM, a dense endomysial weave network consisting of fine fibrils was associated predominantly with collagen type I and III, associated moderately with type VI collagen, but less associated with type IV collagen. Perimysial collagen bundles and collagen strands increased both in number and thickness. The outstanding finding was the presence of giant coiled perimysial fibers measuring about 20-30 microns in diameter. The prominent increase in perimysial fibrosis was closely associated with the accumulation of both type I and type III collagen, and associated moderately with type VI collagen. Interestingly, type V collagen increased in the intracellular matrix of the myocardium in DCM. Type II collagen was not present in either normal or diseased hearts. These structural and immunohistochemical characteristics of collagen may provide insights important to assessing the pathogenesis of the cardiac lesion of DCM.