ADAM-9, ADAM-15, and ADAM-17 are upregulated in macrophages in advanced human atherosclerotic plaques in aorta and carotid and femoral arteries—Tampere vascular study

Author： Oksala Niku Levula Mari Airla Nina Pelto-Huikko Markku Ortiz Rebekka Jarvinen Otso Salenius Juha-Pekka Ozsait Bilge Komurcu-Bayrak Evrim Erginel-Unaltuna Nihan Huovila Ari-Pekka Kytomaki Leena Soini Juhani Kahonen Mika Karhunen Pekka Laaksonen Reijo Lehtimaki Terho

Publisher： Informa Healthcare

ISSN： 0785-3890

Source： Annals of Medicine, Vol.41, Iss.4, 2009-01, pp. : 279-290

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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.