Abstract:
BACKGROUND AND AIMS:The expression of disintegrin and metalloprotease ADAM-9, ADAM-15, and ADAM-17 has been associated with cell-cell, cell-platelet, and cell-matrix interactions and inflammation. They are possibly implicated in the pathophysiology of atherosclerosis. METHODS AND RESULTS:Whole-genome expression array and quantitative real-time polymerase chain reaction (PCR) analysis confirmed that ADAM-9, ADAM-15, and ADAM-17 are upregulated in advanced human atherosclerotic lesions in samples from carotid, aortic, and femoral territories compared to samples from internal thoracic artery (ITA) free of atherosclerotic plaques. Western analysis indicated that the majority of these ADAMs were in the catalytically active form. ADAM-9, ADAM-15, and ADAM-17-expressing cells were shown to co-localize with CD68-positive cells of monocytic origin in the atherosclerotic plaques using immunohistochemistry and double-staining immunofluorescence analysis. Co-localization was demonstrated in all vascular territories. In the carotid territory, cells expressing the ADAMs co-distributed also with smooth muscle cells and, in femoral territory, with CD31-positive endothelial cells, indicating that the ADAM expression pattern depends on vascular bed territory. CONCLUSIONS:Present findings provide strong evidence for the involvement of catalytically active ADAM-9, ADAM-15, and ADAM-17 in advanced atherosclerosis, most notably associated with cells of monocytic origin.
journal_name
Ann Medjournal_title
Annals of medicineauthors
Oksala N,Levula M,Airla N,Pelto-Huikko M,Ortiz RM,Järvinen O,Salenius JP,Ozsait B,Komurcu-Bayrak E,Erginel-Unaltuna N,Huovila AP,Kytömäki L,Soini JT,Kähönen M,Karhunen PJ,Laaksonen R,Lehtimäki Tdoi
10.1080/07853890802649738subject
Has Abstractpub_date
2009-01-01 00:00:00pages
279-90issue
4eissn
0785-3890issn
1365-2060pii
909116860journal_volume
41pub_type
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