Selective deposits of versican in the extracellular matrix of restenotic lesions from human peripheral arteries.

Although a large percentage of the volume of human restenotic arterial lesions is occupied by extracellular matrix (ECM), the composition and organization of this ECM are not well characterized. In this study, restenotic segments taken from 30 human peripheral arteries by directional atherectomy at times ranging from 13 days to 36 months after angioplasty were analyzed for specific patterns of ECM composition and organization by light and electron microscopic histochemistry and immunohistochemistry. Histochemical analysis revealed the presence of distinct zones, enriched either in proteoglycans or fibrillar collagen. Most sections contained these regions juxtaposed to each other. The frequency of these two distinct ECMs did not change as a function of time after angioplasty. The collagen-rich zone usually contained elongated smooth muscle cells spaced close together except in regions resembling fibrous plaques. The proteoglycan-rich ECM contained both elongated and stellate-shaped smooth muscle cells randomly arranged and separated by wide distances. This region resembled the loose-connective-tissue-containing myxoid region typical of restenotic lesions. Immunohistochemical analysis of these regions revealed that the proteoglycan-containing zone stained intensely for versican, a large interstitial chondroitin sulfate proteoglycan, whereas the collagen-containing areas were mostly negative for versican but positive for type I collagen. The versican-positive regions also immunostained for biglycan, a small leucine-rich dermatan sulfate proteoglycan, and sparsely for elastin. However, both of these ECM molecules were present in the versican-negative type I collagen-positive regions of the lesions. These results suggest that the development of restenotic lesions involves localized deposits of specific ECM molecules that may play a role in the asymmetric renarrowing of this tissue after angioplasty.