Possible involvement of notch signaling in the pathogenesis of Buerger's disease
Possible involvement of notch signaling in the pathogenesis of Buerger's disease
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Notch信号传导可能参与布尔格病的发病机制
DOI：
10.1007/s00595-013-0566-9
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Kimihiro Komori
中科院分区：
文献类型：
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作者：
Hiroaki Tamai;Masayoshi Kobayashi;Kyousuke Takeshita;Akio Kodama;Hiroshi Banno;Hiroshi Narita;Kiyohito Yamamoto;Kimihiro Komori
目的在病理条件下，Notch信号通路参与动脉硬化、动脉粥样硬化和缺血性血管新生的炎症过程。本研究的目的是观察是否与Notch信号activation.MethodsAll的患者在1980年至2009年诊断在名古屋大学医院伯格病。采用免疫组化方法对12例Buerger病（TAO）患者的22份标本和9例动脉硬化闭塞症（阿索）患者的13份标本进行Notch 1，Jagged-1（Notch配体）和Hes-1结果Notch 1和Jagged-1在新生血管内皮细胞和中膜平滑肌细胞中均有高表达。这些Notch相关蛋白在TAO患者标本的内膜炎性细胞中也有显著表达。斑块内炎症细胞表达Notch相关蛋白较少（Notch 1（%）：8.4 ± 0.76vs1.3 ± 0.43，P < 0.001; Jagged-1（%）：9.3 ± 1.1vs5.2 ± 1.1，P = 0.03）。事实上，Notch 1下游的转录因子Hes-1在TAO患者的新生毛细血管内皮和炎性细胞中显著表达。TAO组样本的血栓中也观察到Notch 1阳性单核细胞。结论我们的研究结果首次证明炎症细胞中Notch信号激活可能参与了伯格病的病理生理机制。
PurposeUnder pathological conditions, the Notch signal pathway is involved in the inflammatory process in arteriosclerosis, atherosclerosis and angiogenesis under ischemic conditions. The purpose of this study was to observe whether or not Buerger’s disease is associated with Notch signal activation.MethodsAll the patients were diagnosed between 1980 and 2009 at Nagoya University Hospital. Twenty-two specimens from 12 patients with Buerger’s disease (TAO) and 13 specimens from nine patients with arteriosclerosis obliterans (ASO) were analyzed by immunohistochemistry for Notch1, Jagged-1 (a Notch ligand) and Hes-1 (a Notch 1 target transcription factor).ResultsNotch1 and Jagged-1 were highly expressed in the endothelium in the new vasa vasorum and in the smooth muscle cells in the media of specimens from both groups. These Notch-related proteins were also remarkably expressed in inflammatory cells in the intima of specimens from TAO patients. Fewer inflammatory cells expressed Notch-related proteins in atheromatous plaques (Notch1 (%): 8.4 ± 0.76 versus 1.3 ± 0.43,P< 0.001; Jagged-1(%): 9.3 ± 1.1 versus 5.2 ± 1.1,P= 0.03). Indeed, Hes-1, which is a transcription factor downstream of Notch1, was remarkably expressed in the endothelium of new capillary vessels and inflammatory cells in TAO patients. Notch1-positive mononuclear cells were also seen in the thrombus in samples from the TAO group.ConclusionsOur findings are the first demonstration that Notch signal activation in inflammatory cells may be involved in the pathophysiological mechanism underlying Buerger’s disease.