Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Tampere, Finland.
Ann Med. 2010 Jul;42(5):360-70. doi: 10.3109/07853890.2010.486408.
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.
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.
The present findings provide evidence for the involvement of CAs in advanced atherosclerosis in osteoclast-like cells of monocyte-macrophage lineage.
碳酸酐酶（CA）通过催化二氧化碳生成碳酸氢根和质子，在破骨细胞功能和骨重塑中发挥核心作用。根据之前的组织化学研究，进展性动脉粥样硬化斑块与骨骼具有相似性。然而，CA 是否在斑块中表达尚不清楚。
对动脉样本（n=24）进行全基因组表达谱分析，与取自胸内动脉的对照血管样本（n=6）相比，证实了几个指示成骨细胞和破骨细胞生成的基因在斑块中上调，包括 CA2 和 CA12，其表达也通过定量逆转录聚合酶链反应（RT-PCR）得到验证。与对照组相比，在动脉粥样硬化斑块中，CA2 和 CA12 的表达分别上调了 11.6 倍（P < 0.0001）和 11.4 倍（P < 0.0001）。根据定量 PCR，颈动脉（12.3 倍，P < 0.0001）、股动脉（13.2 倍，P < 0.01）和主动脉斑块中 CA2 的表达升高，CA12 的表达在颈动脉（11.6 倍，P < 0.0001）、股动脉（11.5 倍，P < 0.01）和主动脉斑块（9.7 倍，P < 0.0001）中升高。免疫组织化学和双重免疫荧光分析发现，CAII、CAXII 和 CD68 以及抗酒石酸酸性磷酸酶（TRAP），一种破骨细胞样细胞的标志物，在动脉粥样硬化斑块中的多核巨细胞中共同定位。
本研究结果为 CA 在单核巨噬细胞来源的破骨样细胞中参与晚期动脉粥样硬化提供了证据。
