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升主动脉瘤患者的骨桥蛋白和基质金属蛋白酶 2、9 的信使 RNA 表达和血浆蛋白水平升高。

Elevated messenger RNA expression and plasma protein levels of osteopontin and matrix metalloproteinase types 2 and 9 in patients with ascending aortic aneurysms.

机构信息

Institute of Clinical Medicine, Department of Internal Medicine, Clinical Research Center, Oulu University Hospital and Biocenter Oulu, University of Oulu, Oulu, Finland.

Institute of Clinical Medicine, Department of Internal Medicine, Clinical Research Center, Oulu University Hospital and Biocenter Oulu, University of Oulu, Oulu, Finland.

出版信息

J Thorac Cardiovasc Surg. 2013 Apr;145(4):1117-1123. doi: 10.1016/j.jtcvs.2012.04.008. Epub 2012 May 7.

Abstract

OBJECTIVE

Ascending aortic aneurysms result from a degenerative process in the aortic wall, characterized by the loss of smooth muscle cells and elastic fibers. We hypothesized that there would be changes in plasma protein and aortic tissue messenger RNA levels of osteopontin, matrix metalloproteinase type 2, matrix metalloproteinase type 9, and tissue inhibitor of matrix metalloproteinases type 1 in ascending aortic aneurysm samples.

METHODS

Plasma, aortic tissue, and aortic mRNA samples were collected from patients with an ascending aortic aneurysm or an abdominal aortic aneurysm and from control individuals. Plasma protein levels of osteopontin, matrix metalloproteinase (MMP) types 2 and 9, and tissue inhibitor of matrix metalloproteinases type 1 were determined by quantitative sandwich enzyme-linked immunosorbent assay. Aortic mRNA levels of these same proteins were analyzed with the quantitative real-time polymerase chain reaction (RT-PCR) method and protein levels from the aortic tissues were assayed by immunostaining. Quantitative RT-PCR results were estimated by the normalized expression method (ΔΔCt).

RESULTS

Plasma protein levels were significantly elevated for osteopontin, MMP-2, and MMP-9 in the samples of ascending and abdominal aortic aneurysm group compared with controls. Plasma protein levels of MMP-9 were higher in the nonoperated compared with the operated ascending aortic aneurysm group. Aortic osteopontin, MMP-2, and MMP-9 mRNA levels were increased for ascending aortic aneurysm samples.

CONCLUSIONS

This study reveals an important role of osteopontin, MMP-2 and MMP-9 in the development of ascending and abdominal aortic aneurysm.

摘要

目的

升主动脉瘤是由于主动脉壁的退行性病变引起的,其特征是平滑肌细胞和弹性纤维的丧失。我们假设在升主动脉瘤样本中,血浆蛋白和主动脉组织信使 RNA 水平的骨桥蛋白、基质金属蛋白酶 2、基质金属蛋白酶 9 和基质金属蛋白酶组织抑制剂 1 会发生变化。

方法

从升主动脉瘤或腹主动脉瘤患者以及对照个体中采集血浆、主动脉组织和主动脉 mRNA 样本。通过定量夹心酶联免疫吸附试验测定血浆骨桥蛋白、基质金属蛋白酶(MMP)2 和 9 以及基质金属蛋白酶组织抑制剂 1 的蛋白水平。用定量实时聚合酶链反应(RT-PCR)方法分析这些相同蛋白的主动脉 mRNA 水平,并通过免疫染色测定主动脉组织中的蛋白水平。用标准化表达法(ΔΔCt)估计定量 RT-PCR 结果。

结果

与对照组相比,升主动脉瘤和腹主动脉瘤组的血浆蛋白水平显著升高,骨桥蛋白、MMP-2 和 MMP-9。未手术的升主动脉瘤组与手术的升主动脉瘤组相比,MMP-9 的血浆蛋白水平更高。升主动脉瘤样本的主动脉骨桥蛋白、MMP-2 和 MMP-9 mRNA 水平增加。

结论

本研究揭示了骨桥蛋白、MMP-2 和 MMP-9 在升主动脉瘤和腹主动脉瘤发展中的重要作用。

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