Oksala Niku, Levula Mari, Airla Nina, Pelto-Huikko Markku, Ortiz Rebekka M, Järvinen Otso, Salenius Juha-Pekka, Ozsait Bilge, Komurcu-Bayrak Evrim, Erginel-Unaltuna Nihan, Huovila Ari-Pekka J, Kytömäki Leena, Soini Juhani T, Kähönen Mika, Karhunen Pekka J, Laaksonen Reijo, Lehtimäki Terho
Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland.
Ann Med. 2009;41(4):279-90. doi: 10.1080/07853890802649738.
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.
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.
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.
解聚素和金属蛋白酶ADAM - 9、ADAM - 15及ADAM - 17的表达与细胞 - 细胞、细胞 - 血小板及细胞 - 基质相互作用以及炎症相关。它们可能参与动脉粥样硬化的病理生理学过程。
全基因组表达阵列及定量实时聚合酶链反应（PCR）分析证实，与无动脉粥样硬化斑块的胸廓内动脉（ITA）样本相比，在来自颈动脉、主动脉和股动脉区域样本的晚期人类动脉粥样硬化病变中，ADAM - 9、ADAM - 15及ADAM - 17表达上调。蛋白质免疫印迹分析表明，这些ADAMs中的大多数处于催化活性形式。使用免疫组织化学和双染免疫荧光分析显示，在动脉粥样硬化斑块中，表达ADAM - 9、ADAM - 15及ADAM - 17的细胞与单核细胞来源的CD68阳性细胞共定位。在所有血管区域均证实了共定位。在颈动脉区域，表达ADAMs的细胞也与平滑肌细胞共分布，而在股动脉区域，则与CD31阳性内皮细胞共分布，这表明ADAM的表达模式取决于血管床区域。
目前的研究结果为催化活性的ADAM - 9、ADAM - 15及ADAM - 17参与晚期动脉粥样硬化提供了有力证据，最显著的是与单核细胞来源的细胞相关。
