BACKGROUND AND AIMS: 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. METHODS AND 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.
BACKGROUND AND AIMS: 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. METHODS AND 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.
Authors: Yue-Mei Fan; Jussi Hernesniemi; Niku Oksala; Mari Levula; Emma Raitoharju; Auni Collings; Nina Hutri-Kähönen; Markus Juonala; Jukka Marniemi; Leo-Pekka Lyytikäinen; Ilkka Seppälä; Ari Mennander; Matti Tarkka; Antti J Kangas; Pasi Soininen; Juha Pekka Salenius; Norman Klopp; Thomas Illig; Tomi Laitinen; Mika Ala-Korpela; Reijo Laaksonen; Jorma Viikari; Mika Kähönen; Olli T Raitakari; Terho Lehtimäki Journal: Sci Rep Date: 2014-04-11 Impact factor: 4.379
Authors: Matthew Traylor; Kari-Matti Mäkelä; Laura L Kilarski; Elizabeth G Holliday; William J Devan; Mike A Nalls; Kerri L Wiggins; Wei Zhao; Yu-Ching Cheng; Sefanja Achterberg; Rainer Malik; Cathie Sudlow; Steve Bevan; Emma Raitoharju; Niku Oksala; Vincent Thijs; Robin Lemmens; Arne Lindgren; Agnieszka Slowik; Jane M Maguire; Matthew Walters; Ale Algra; Pankaj Sharma; John R Attia; Giorgio B Boncoraglio; Peter M Rothwell; Paul I W de Bakker; Joshua C Bis; Danish Saleheen; Steven J Kittner; Braxton D Mitchell; Jonathan Rosand; James F Meschia; Christopher Levi; Martin Dichgans; Terho Lehtimäki; Cathryn M Lewis; Hugh S Markus Journal: PLoS Genet Date: 2014-07-31 Impact factor: 5.917