Age related changes of the collagen network of the human heart

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Abstract

The objective of this work was to study the collagen tissue of the human heart muscle as a function of age. The types of collagen, their disposition, as well as the density of collagen tissue and diameter of collagen fibrils were examined. Pieces of the ventricular wall from 12 human hearts, six from young individuals and six from aged individuals were studied by the Picrosirius–polarization method and by transmission electron microscopy (TEM). The results obtained showed the presence of two types of collagen fibers in the ventricular walls — thin, weakly birefringent, greenish fibers (collagen type III) and thick, yellow or red, strongly, birefringent fibers (collagen type I), both in the endomysium and perimysium. In the hearts obtained from old subjects, there were no significant differences in the arrangement of the collagen fibers in relation to the hearts obtained from young subjects. Measurements of collagen content in myocardial tissue suggest that both perimysial and endomysial collagen type I fibers increase in number and thickness in the old. These histochemical results obtained coincided with the electron microscopic observations in showing increase in the number of collagen fibrils with large diameter in the old hearts. These ultrastructural and histochemical characteristics of collagen may provide insights important to assessing the pathogenesis of the cardiac lesions of several cardiopathies in the aged heart.

Introduction

The interstitial collagen matrix is an important component of the myocardium, which surrounds and supports cardiac myocytes and the coronary microcirculation (Borg and Caufield, 1981, Robinson et al., 1983). The interstitial collagen also maintains the myocytes alignment, the myocyte–capillary relationship, and the heart architecture throughout the cardiac cycle (Borg and Caufield, 1981). Therefore, the form and distribution of the connective tissue of the heart is such that it may play an important role in the elastic properties and viscous properties of the left ventricle. The major types of collagen present in the interstitium of myocardium are I, III and V, with type I predominating. In non-human primate myocardium, for example, the distribution of collagen types is as follows, 85% type I; 11% type III and 3% type V (Weber et al., 1988). In the myocardium, fibers which surround large bundles of myocytes and individual myocytes appear to be a copolymerization of the I and III collagen molecules (Contard et al., 1991).

Collagen is the only protein in the organism showing definite age changes. A relationship with the general process of aging has, therefore, been assumed. Physicochemical changes in the chemical and thermic contraction have been demonstrated in collagen fibers of different ages (Chvapil and Hruza, 1959, Werzár, 1964). Moreover, biochemical changes in the tissues such as a decrease in the content of extractable collagen (Boucek et al., 1958, Kao and MacGavack, 1959, Koberle and Chvapil, 1962, Wirtschaftler and Bentley, 1962) show a relationship with increasing age, and the total collagen content in certain tissues has been found to increase with age (Sobel and Marmorston, 1956, Clausen, 1963, Gomes et al., 1997, Akamatsu et al., 1999).

In order to understand the changes in the human myocardial tissue in disease, a knowledge of their detailed structure in the normal state is required. However, there have been few studies on the aging of collagen in the human heart. The aim of the present investigation was to determine the types of collagen, to measure the collagen content and the collagen fibril diameters of the left ventricle of the human heart and to observe any differences between young and aged.

Section snippets

Materials and methods

Twelve human hearts obtained at necropsy from male individuals aged 20–25 (young group, n=6) and 67–87 (aged group, n=6) with no earlier pathologies were used. From the esternocostal region of the left ventricle, a segment of 2 cm2 was obtained.

Young group

Collagen fibers of the myocardium formed an intricate and highly structured network. In the hearts of the young group, in sections stained with Picrossirius and observed with polarization microscopy, the perimysium presents thick, yellow or red, strongly birefringent collagen fibers, characteristic of collagen type I and also thin, pale fibers of greenish color, typical of collagen type III (Fig. 1A). The endomysium, which lies between cardiac myocites, presented the same composition, but with

Discussion

In our study, we demonstrated that polarized light facilitates quantitative image analysis of collagen. When examined in bright field, collagen appears red and muscle yellow after Picrosirius red staining. This brightfield contrast between collagen and muscle has been used, in conjunction with digital image analysis, to assess myocardial collagen content (Michel et al., 1986). However, it is the combination of Picrosirius red and polarized light microscopy that provides a more powerful method

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