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Ephrin-B1及其同源受体EphB2在人腹主动脉瘤中的表达与功能

Expression and Function of Ephrin-B1 and Its Cognate Receptor EphB2 in Human Abdominal Aortic Aneurysm.

作者信息

Sakamoto Aiji, Kawashiri Masaaki, Ishibashi-Ueda Hatsue, Sugamoto Yuka, Yoshimuta Tsuyoshi, Higashikata Takeo, Ogino Hitoshi, Tada Hayato, Konno Tetsuo, Hayashi Kenshi, Yamagishi Masakazu

机构信息

Department of Vascular Physiology, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.

出版信息

Int J Vasc Med. 2012;2012:127149. doi: 10.1155/2012/127149. Epub 2012 Jul 5.

Abstract

We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis, in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7% (P = 0.01) and 50.7 ± 13.1% (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought.

摘要

我们检测了人腹主动脉瘤(AAA)中血管生成和胚胎发育的关键调节因子ephrin-B1及其同源受体EphB2的表达,并分析了它们在细胞迁移中的功能作用。从10例行AAA血管手术的患者(9例男性,1例女性;年龄68.5±2.4岁)中获取AAA组织及相邻对照组织。采用实时逆转录聚合酶链反应(RT-PCR)分析ephrin-B1和EphB2的表达。我们还通过组织学方法确定了这些分子在AAA组织中的定位。最后,通过细胞迁移试验检测ephrin-B1和EphB2对炎性细胞趋化性的影响。与正常对照相比,AAA中ephrin-B1(0.410±0.046对1.198±0.252,P = 0.027)和EphB2(0.764±0.212对1.272±0.137,P = 0.594)的表达水平更高。ephrin-B1和EphB2均在AAA内的巨噬细胞、T淋巴细胞和内皮细胞中表达。在趋化试验中,ephrin-B1和EphB2分别将基质衍生因子-1诱导的单核细胞趋化性抑制至54.7±12.7%(P = 0.01)和50.7±13.1%(P = 0.01)。这些数据表明,ephrin-B1和EphB2可能在人类成人炎性细胞中发挥作用,并参与AAA的发病机制,尽管这些分子的具体作用仍有待进一步研究。

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