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 an d organization of this ECM are not well characterized In this study, r estenotic segments taken from 30 human peripheral arteries by directio nal atherectomy at times ranging from 13 days to 36 months after angio plasty were analyzed for specific patterns of ECM composition and orga nization by light and electron microscopic histochemistry and immunohi stochemistry. Histochemical analysis revealed the presence of distinct zones, enriched either in proteoglycans or fibrillar collagen, Most s ections contained these regions juxtaposed to each other, The frequenc y of these two distinct ECMs did not change as a function of time afte r angioplasty, The collagen-rich zone usually contained elongated smoo th muscle cells spaced close together except in regions resembling fib rous plaques, The proteoglycan-rich ECM contained both elongated and s tellate-shaped smooth muscle cells randomly arranged and separated by wide distances, This region resembled the loose-connective-tissue-cont aining myxoid region typical of restenotic lesions. Immunohistochemica l 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 mostl y negative for versican but positive for type I collagen. The versican -positive regions also immunostained for biglycan, a small leucine-ric h dermatan sulfate proteoglycan, and sparsely for elastin, However, bo th 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 s pecific ECM molecules that may play a role in the asymmetric renarrowi ng of this tissue after angioplasty.