Abstract:
:Since accumulation and interaction of immune cells including T cells and monocytes/macrophages are involved in the processes of atherosclerosis, atherosclerosis is currently understood as an inflammatory disorder. Entrapment of extracellular matrices components such as hyaluronan by monocytes and macrophages, as well as uptake of oxidized low-density lipoprotein (ox-LDL) by these cells, plays a central role in foam cell formation and the pathogenesis of atherosclerosis. We investigated the role of CD44, the principal receptor for hyaluronic acid, and ox-LDL in scavenger receptor expression on resting monocytes prepared by counterflow centrifugal elutriation from the endothelium. Our results showed that the low-molecular weight (6.9 kDa) form of hyaluronan increased the expression of CD36 scavenger receptor; the incorporation of (125) I-labeled ox-LDL, and the transendothelial migration of monocytes, which were mediated at least in part via tyrosine kinase and the PKC pathway. Our results imply that low molecular weight hyaluronan produced in large amounts in atherosclerotic lesions induces differentiation of circulating monocytes to macrophages/foam cells and enhances the progression of atherosclerosis via the PKC pathway. Furthermore, low molecular weight hyaluronan also amplifies the migration of monocytes into inflamed atherosclerotic plaques. Thus, we propose that engagement of CD44 with low molecular weight hyaluronan is centrally involved in the inflammatory pathogenesis of athelosclerotic plaques through migration of monocytes and foamed macrophage differentiation.
journal_name
Endocr Jjournal_title
Endocrine journalauthors
Tabata T,Mine S,Okada Y,Tanaka Ydoi
10.1507/endocrj.k05-120subject
Has Abstractpub_date
2007-12-01 00:00:00pages
685-93issue
5eissn
0918-8959issn
1348-4540pii
JST.JSTAGE/endocrj/K05-120journal_volume
54pub_type
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