Carbonic anhydrases II and XII are up-regulated in osteoclast-like cells in advanced human atherosclerotic plaques-Tampere Vascular Study.
OBJECTIVE
Carbonic anhydrases (CA) play a central role in osteoclast function and bone remodeling by catalyzing the formation of bicarbonate and proton from carbon dioxide. According to previous histochemical studies, advanced atherosclerotic plaques share similarities with bone. However, whether CAs are expressed in plaques is not known.


RESULTS
Whole genome expression array of arterial samples (n = 24) confirmed that several genes indicating osteoblastogenesis and osteoclastogenesis were up-regulated in plaques when compared to control vessel samples from internal thoracic arteries (n = 6), including CA2 and CA12, expression of which was also verified with quantitative reverse transcription polymerase chain reaction (RT-PCR). In atherosclerotic plaques there was 11.6-fold (P < 0.0001) and 11.4-fold (P < 0.0001) up-regulation of CA2 and CA12, compared to controls, respectively. According to quantitative PCR, CA2 expression was elevated in carotid (12.3-fold, P < 0.0001), femoral (13.2-fold, P < 0.01), and aortic plaques (7.5-fold, P < 0.0001). CA12 expression was elevated in carotid (11.6-fold, P < 0.0001), femoral (11.5-fold, P < 0.01), and aortic plaques (9.7-fold, P < 0.0001). CAII, CAXII, and CD68 and tartrate-resistant acid phosphatase (TRAP), a marker of osteoclast-like cells, were found to be co-localized in multinucleated giant cells in the atherosclerotic plaques using immunohistochemistry and double-staining immunofluorescence analysis.


CONCLUSIONS
The present findings provide evidence for the involvement of CAs in advanced atherosclerosis in osteoclast-like cells of monocyte-macrophage lineage.
Oksala
Niku
N
Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Tampere, Finland. niku.oksala@tuubi1.net
Levula
Mari
M
Pelto-Huikko
Markku
M
Kytömäki
Leena
L
Soini
Juhani T
JT
Salenius
Juha
J
Kähönen
Mika
M
Karhunen
Pekka J
PJ
Laaksonen
Reijo
R
Parkkila
Seppo
S
Lehtimäki
Terho
T
D000135:Acid Phosphatase / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D024402:Carbonic Anhydrase II / Q000235:genetics*; D002256:Carbonic Anhydrases / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D015726:Giant Cells / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071681:Tartrate-Resistant Acid Phosphatase; D015854:Up-Regulation; D000097382:CD68 Molecule
D000135:Acid Phosphatase; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases; D007527:Isoenzymes; D000071681:Tartrate-Resistant Acid Phosphatase; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C477378:carbonic anhydrase XII