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Original Article

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

Niku Oksala Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland; Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, FinlandCorrespondence[email protected]

, PhD , MD,

Mari Levula Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland

,

Nina Airla Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland

,

Markku Pelto-Huikko Department of Developmental Biology, Medical School, University of Tampere and Department of Pathology, Tampere University Hospital, Finland

,

Rebekka M. Ortiz Institute of Medical Technology, University of Tampere, and Department of Pathology, Tampere, University Hospital, Finland

,

Otso Järvinen Heart Center, Department of Cardiac Surgery, Tampere University Hospital, Finland

,

Juha-Pekka Salenius Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Finland

,

Bilge Ozsait Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland; Department of Genetics, Institute for Experimental Medicine, Istanbul University, Turkey

,

Evrim Komurcu-Bayrak Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland; Department of Genetics, Institute for Experimental Medicine, Istanbul University, Turkey

,

Nihan Erginel-Unaltuna Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland; Department of Genetics, Institute for Experimental Medicine, Istanbul University, Turkey

,

Ari-Pekka J. Huovila Institute of Medical Technology, University of Tampere, and Department of Pathology, Tampere, University Hospital, Finland

,

Leena Kytömäki Turku Center for Biotechnology, Turku, Finland

,

Juhani T. Soini Turku Center for Biotechnology, Turku, Finland

,

Mika Kähönen Department of Physiology, Tampere University Hospital, Finland

,

Pekka J. Karhunen Department of Forensic Medicine, University of Tampere, Finland

,

Reijo Laaksonen Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland

&

Terho Lehtimäki Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland

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.

Keywords

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