title: Activation of the non-receptor tyrosine kinase cSrc in macrophage-rich atherosclerotic plaques of human carotid arteries.
abstract: To determine the involvement of the non-receptor tyrosine kinase cSrc in plaque destabilization in carotid atherosclerosis (CAS), which is responsible for cerebral infarction, we performed quantitative and morphological detection of phosphorylated active cSrc (p-cSrc) and histopathological examination in CAS lesions. We examined carotid endarterectomy specimens obtained from 32 CAS patients. Each specimen was used for immunoblot and immunohistochemical analyses of p-cSrc, histopathological analysis, and image analysis of macrophage content. There was a strong positive correlation between cSrc activation on blots and macrophage content on sections. When we defined the macrophage-rich plaque (MRP) and the macrophage-poor plaque (MPP) as having macrophage content more and less than 5%, respectively, the p-cSrc density and the occurrence of plaque hemorrhage and thrombus formation were significantly increased in the MRP group (n=18) compared to the MPP group (n=14). p-cSrc immunoreactivity was localized in lesional endothelial cells, macrophages, and smooth muscle cells, which contained proinflammatory substances: the upstream oxidized low density lipoprotein, tissue factor and osteopontin, and the downstream active forms of extracellular signal-activated kinase and p38 and nuclear factor-kappaB. Our results suggest that cSrc activation in lesional cells contributes to plaque destabilization in CAS via persistent inflammation.
authors.affiliation: Department of Neurology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Sono
authors.initials: S
authors.lastname: Toi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shibata
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Sawada
authors.forename: Makio
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Uchiyama