Structural Heterogeneity of the Diffuse Intimal Thickening and Correlation with Distribution of TGF-β1

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Abstract
This study examines the ultrastructural features of diffuse intimal thickenings of human coronary arteries and correlates structural heterogeneity along the radial axis with the distribution and known actions of transforming growth factor β1 (TGF-β1). Morphometric and immunohistochemical data were collected from thickenings of varying widths, sampled at autopsy from 19 persons ranging in age from 3 months to 81 years. Thickenings were characterised by an inner proteoglycan layer (PGL), up to ∼ 70 mm wide, and an underlying variable-width musculofibrous layer (MFL). The PGL was characterised by low volume fractions (v/fs) for collagen, elastin, basement membranes and cells and a high v/f for matrix space; v/fs for the MFL components were more evenly distributed. Proteoglycans were visualised by ruthenium red staining, quantified and sized. Densities of large (versican;>20nm) and small (1 staining was detected in 70% of vessels examined and occurred almost exclusively in the PGL, although showed a patchy distribution. Both the distribution of TGF-β1 and its known differential effects on versican and decorin synthesis suggest that it may play a significant role in the formation and maintenance of the PGL.

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