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CXCR4:腹主动脉瘤壁炎症活动的潜在标志物。

CXCR4: A Potential Marker for Inflammatory Activity in Abdominal Aortic Aneurysm Wall.

作者信息

Tanios F, Pelisek J, Lutz B, Reutersberg B, Matevossian E, Schwamborn K, Hösel V, Eckstein H-H, Reeps C

机构信息

Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Munich, Germany.

Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Munich, Germany.

出版信息

Eur J Vasc Endovasc Surg. 2015 Dec;50(6):745-53. doi: 10.1016/j.ejvs.2015.07.040. Epub 2015 Sep 4.

Abstract

OBJECTIVES

The aim of the study was to evaluate the potential role of chemokine receptor CXCR4 and its ligand CXCL12 in the pathogenesis of abdominal aortic aneurysm (AAA).

METHODS

AAA tissue specimens were obtained from the anterior or lateral aneurysm sac of patients (n = 32, 26 males, 6 females; 66.8 ± 11.2 years, diameter 64.4 ± 17.0 mm), who underwent elective open surgical repair. Twelve non-aneurysmal aortic specimens from transplant donors served as controls. Expression analysis of CXCR4 and CXCL12 at mRNA and protein level was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Immunohistochemical staining of corresponding histological sections for CD3 (T-cells), CD20 (B-cells), and CD68 (macrophages) was performed to determine the cellular localization of CXCR4 and CXCL12. Data were analyzed with SPSS 20.0 using Mann-Whitney U test and Spearman's rank correlation coefficient.

RESULTS

Gene expression of CXCR4 and CXCL12 was 9.6 and 4.6 fold higher in AAA than in non-aneurysmal aorta (p = .0004 and p < .0001, respectively). Likewise, the protein level of CXCR4 was increased 3.2 fold in AAA wall compared with non-aneurysmal aortic tissue (p < .0001), although CXCL12 could not be detected. Immunohistochemical analysis revealed that CXCR4 was expressed in B and T lymphocytes and macrophages, and CXCL12 was observed only in plasma cells.

CONCLUSIONS

This study confirmed the over expression of CXCR4 in human AAA tissue. CXCR4 was detected both at the mRNA and the protein level and by immunohistochemistry, especially in inflammatory cells. In contrast, CXCL12 expression was observed only at the mRNA level, with the exception of plasma cells. The exact role of CXCR4/CXCL12 in AAA has to be further elucidated.

摘要

目的

本研究旨在评估趋化因子受体CXCR4及其配体CXCL12在腹主动脉瘤(AAA)发病机制中的潜在作用。

方法

从接受择期开放手术修复的患者(n = 32,男26例,女6例;年龄66.8±11.2岁,直径64.4±17.0 mm)的动脉瘤前壁或侧壁获取AAA组织标本。取12例移植供体的非动脉瘤性主动脉标本作为对照。通过定量逆转录-聚合酶链反应(RT-PCR)和蛋白质印迹法测定CXCR4和CXCL12在mRNA和蛋白质水平的表达分析。对相应组织切片进行CD3(T细胞)、CD20(B细胞)和CD68(巨噬细胞)的免疫组织化学染色,以确定CXCR4和CXCL12的细胞定位。使用SPSS 20.0软件,采用曼-惠特尼U检验和斯皮尔曼等级相关系数对数据进行分析。

结果

CXCR4和CXCL12的基因表达在AAA中分别比非动脉瘤性主动脉高9.6倍和4.6倍(p分别为0.0004和p < 0.0001)。同样,与非动脉瘤性主动脉组织相比,AAA壁中CXCR4的蛋白质水平增加了3.2倍(p < 0.0001),尽管未检测到CXCL12。免疫组织化学分析显示,CXCR4在B淋巴细胞、T淋巴细胞和巨噬细胞中表达,而CXCL12仅在浆细胞中观察到。

结论

本研究证实了CXCR4在人AAA组织中的过度表达。通过RT-PCR、蛋白质印迹法及免疫组织化学方法均检测到CXCR4,尤其在炎症细胞中。相比之下,除浆细胞外,CXCL12仅在mRNA水平表达。CXCR4/CXCL12在AAA中的确切作用有待进一步阐明。

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