title: Active macrophage-associated TGF-beta co-localizes with type I procollagen gene expression in atherosclerotic human pulmonary arteries.
abstract: Vascular remodeling in adult atherosclerotic pulmonary arteries is characterized by discrete areas of neointimal smooth muscle cell extracellular matrix gene expression in close proximity to non-foamy macrophages, suggesting regulation by local macrophage-associated factors. The purpose of these studies was to begin addressing the role of putative macrophage-associated factors such as transforming growth factor-beta (TGF-beta), by determining the spatial relationship between TGF-beta and neointimal matrix gene expression in human atherosclerotic pulmonary arteries. For example, the participation of TGF-beta in vascular remodeling could be inferred by its colocalization with non-foamy macrophages in areas of active matrix synthesis. In situ hybridization and immunohistochemistry demonstrated focal neointimal procollagen gene expression in close association with non-foamy but not foamy macrophages. Immunohistochemistry with isoform-specific anti-TGF-beta antibodies demonstrated all three isoforms of TGF-beta associated with non-foamy macrophages, but foamy macrophages were not immunoreactive. Neointimal and medial smooth muscle cells stained lightly. In contrast, intense TGF-beta immunoreactivity was also associated with medial smooth muscle cells in normal nonremodeling vessels. Immunohistochemistry with antibodies specific for latent TGF-beta was similar to immunohistochemistry for mature TGF-beta in both remodeling and nonremodeling vessels. Finally, using an antibody specific for active TGF-beta 1, immunoreactivity was only seen in non-foamy neointimal macrophages but not in foamy macrophages or medial smooth muscle cells from hypertensive or normal vessels. These observations suggest non-foamy macrophages may participate in modulating matrix gene expression in atherosclerotic remodeling via a TGF-beta-dependent mechanism.
authors.affiliation: Respiratory and Critical Care Division, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bahadori
authors.forename: J
authors.initials: J
authors.lastname: Milder
authors.forename: L
authors.initials: L
authors.lastname: Gold
authors.forename: M
authors.initials: M
authors.lastname: Botney
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008264:Macrophages / Q000276:immunology*; D011347:Procollagen / Q000032:analysis* / Q000235:genetics; D011651:Pulmonary Artery / Q000737:chemistry* / Q000276:immunology / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000032:analysis*
chemical_list: D011347:Procollagen; D016212:Transforming Growth Factor beta