PROTEOGLYCAN DISTRIBUTION IN LESIONS OF ATHEROSCLEROSIS DEPENDS ON LESION SEVERITY, STRUCTURAL CHARACTERISTICS, AND THE PROXIMITY OF PLATELET-DERIVED GROWTH-FACTOR AND TRANSFORMING-GROWTH-FACTOR-BETA

The accumulation of proteoglycans (PGs) in atherosclerosis contributes to disease progression and stenosis and may partly depend on local re gulation by growth factors such as platelet-derived growth factor (PDG F) and transforming growth factor (TGF)-beta. In this study, the distr ibution of the major extracellular PGs is compared with that of PDGF a nd TGF-beta isoforms in developing lesions of atherosclerosis from hyp ercholesterolemic nonhuman primates, Strong immunostaining for decorin , biglycan, versican, and hyaluronan is observed in both intermediate and advanced lesions, Perlecan staining is weak in intermediate lesion s but strong in advanced lesions in areas bordering the plaque core, I mmunostaining for PDGF-B and TGF-beta 1 is particularly prominent in m acrophages in intermediate and advanced lesions, In contrast, TGF-beta 2 and TGF-beta 3 and PDGF-A are present in both macrophages and smoot h muscle cells. Overall, PG deposits parallel areas of intense growth factor immunostaining, with trends in relative localization that sugge st interrelationships among certain PGs and growth factors, Notably, d ecorin and TGF-beta 1 are distributed similarly, predominantly in the macrophage-rich core, whereas biglycan is prominent in the smooth musc le cell matrix adjoining TGF-beta 1-positive macrophages. Versican and hyaluronan are enriched in the extracellular matrix adjacent to both PDGF-and TGF-beta 1-positive cells. These data demonstrate that PG acc umulation varies with lesion severity, structural characteristics, and the proximity of PDGF and TGF-beta.