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.
OBJECTIVE
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.


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.
Oksala
Niku
N
Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland. niku.oksala@tuubi1.net
Levula
Mari
M
Airla
Nina
N
Pelto-Huikko
Markku
M
Ortiz
Rebekka M
RM
Järvinen
Otso
O
Salenius
Juha-Pekka
JP
Ozsait
Bilge
B
Komurcu-Bayrak
Evrim
E
Erginel-Unaltuna
Nihan
N
Huovila
Ari-Pekka J
AP
Kytömäki
Leena
L
Soini
Juhani T
JT
Kähönen
Mika
M
Karhunen
Pekka J
PJ
Laaksonen
Reijo
R
Lehtimäki
Terho
T
D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000378:metabolism*; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D008565:Membrane Proteins; D012333:RNA, Messenger; D051722:ADAM Proteins; C098660:ADAM15 protein, human; C098339:ADAM9 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human