循环干扰素-γ诱导的 Cys-X-Cys 趋化因子受体 3 配体在患有主动脉瘤的人类中升高，Cys-X-Cys 趋化因子受体 3 对于小鼠的动脉瘤形成是必需的。
Circulating interferon-γ-inducible Cys-X-Cys chemokine receptor 3 ligands are elevated in humans with aortic aneurysms and Cys-X-Cys chemokine receptor 3 is necessary for aneurysm formation in mice.
机构信息
Department of Surgery, Stanford University, Palo Alto, CA, USA.
出版信息
J Thorac Cardiovasc Surg. 2012 Mar;143(3):704-10. doi: 10.1016/j.jtcvs.2011.08.036. Epub 2011 Sep 29.
OBJECTIVE
Inflammation is associated with the formation of aortic aneurysm. This study investigates the role of inducible Cys-X-Cys chemokine receptor 3 and its ligands in the pathogenesis of arterial aneurysms.
METHODS
Plasma samples from patients with or without a diagnosis of thoracic aortic aneurysms were analyzed by enzyme-linked immunosorbent assay for the T-helper 1 cytokine interferon-γ and the interferon-γ-inducible chemokine receptor 3 ligands: interferon-inducible protein-10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by interferon gamma. Patient charts were reviewed for demographics, initial aortic diameter, and growth rates. Aneurysm diameter and growth rates were correlated with plasma cytokine and chemokine levels using linear regression analysis. We used an animal model of aneurysm formation, where calcium chloride is applied topically to the carotid arteries of wild-type and Cys-X-Cys chemokine receptor 3(-/-) mice. After 10 weeks, the arteries were harvested and analyzed by histology and immunohistochemistry.
RESULTS
Patients with thoracic aortic aneurysms had significant elevations in circulating interferon-γ, interferon-inducible protein-10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by interferon gamma compared with referent patients (P < .001). Cytokine and chemokine plasma levels did not correlate with aneurysm size or growth rates. Cys-X-Cys chemokine receptor 3(-/-) mice were protected from aneurysm formation and showed decreased vascular infiltration by CD45(+) leukocytes.
CONCLUSIONS
Elevated plasma levels of interferon-γ and Cys-X-Cys chemokine receptor 3-binding chemokines are present in patients with thoracic aortic aneurysms. The Cys-X-Cys chemokine receptor 3 receptor is necessary for vascular inflammation and the formation of arterial aneurysms in mice.
目的
炎症与主动脉瘤的形成有关。本研究探讨了诱导型 Cys-X-Cys 趋化因子受体 3 及其配体在动脉瘤发病机制中的作用。
方法
采用酶联免疫吸附试验检测 T 辅助 1 细胞因子干扰素-γ和干扰素-γ诱导的趋化因子受体 3 配体：干扰素诱导蛋白-10、干扰素诱导的 T 细胞α趋化因子和干扰素γ诱导的单核细胞趋化蛋白-1 在有或无胸主动脉瘤诊断的患者的血浆样本中的水平。查阅患者病历，记录人口统计学资料、初始主动脉直径和生长速度。采用线性回归分析将动脉瘤直径和生长速度与血浆细胞因子和趋化因子水平相关联。我们使用动脉瘤形成的动物模型，即用氯化钙局部应用于野生型和 Cys-X-Cys 趋化因子受体 3(-/-) 小鼠的颈动脉。10 周后，采集动脉并通过组织学和免疫组织化学进行分析。
结果
与参照患者相比，患有胸主动脉瘤的患者循环中干扰素-γ、干扰素诱导蛋白-10、干扰素诱导的 T 细胞α趋化因子和干扰素γ诱导的单核细胞趋化蛋白-1 的水平显著升高（P<.001）。细胞因子和趋化因子的血浆水平与动脉瘤大小或生长速度无关。Cys-X-Cys 趋化因子受体 3(-/-) 小鼠免受动脉瘤形成的影响，并显示血管浸润的 CD45(+)白细胞减少。
结论
患有胸主动脉瘤的患者血浆中存在高水平的干扰素-γ和 Cys-X-Cys 趋化因子受体 3 结合趋化因子。Cys-X-Cys 趋化因子受体 3 受体是小鼠血管炎症和动脉瘤形成所必需的。
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