Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene.
Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene.
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DOI：
10.1084/jem.191.2.303
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发表时间：
2000-01-17
期刊：
影响因子：
--
通讯作者：
Duff GW
中科院分区：
文献类型：
--
作者：
Nicklin MJ;Hughes DE;Barton JL;Ure JM;Duff GW
长期以来，高压动脉系统中的分支点和弯曲处一直被认为是异常高湍流的部位，因此在人类中，随之而来的应力是动脉粥样硬化病变的焦点。我们发现，编码内源性抗炎细胞因子白介素1受体拮抗剂(IL-1ra)的基因零突变纯合的小鼠，会发生致命性动脉炎症，累及主动脉及其初级和次级分支的分支点和弯曲。我们观察到大量的中性粒细胞、巨噬细胞和CD4+T细胞的跨壁渗透。动物似乎死于血管壁坍塌、狭窄和器官梗塞，或死于破裂动脉瘤的出血。杂合子不会在出生一年内死于动脉炎，但确实会出现小病变，这表明IL-1ra水平的降低不足以完全控制动脉中的炎症。我们的结果显示，IL-1ra在控制结构性应激动脉壁的自发性炎症中具有令人惊讶的特异性作用，这表明IL-1的表达可能在传递动脉壁损伤信号方面发挥重要作用。
Branch points and flexures in the high pressure arterial system have long been recognized as sites of unusually high turbulence and consequent stress in humans are foci for atherosclerotic lesions. We show that mice that are homozygous for a null mutation in the gene encoding an endogenous antiinflammatory cytokine, interleukin 1 receptor antagonist (IL-1ra), develop lethal arterial inflammation involving branch points and flexures of the aorta and its primary and secondary branches. We observe massive transmural infiltration of neutrophils, macrophages, and CD4+ T cells. Animals appear to die from vessel wall collapse, stenosis, and organ infarction or from hemorrhage from ruptured aneurysms. Heterozygotes do not die from arteritis within a year of birth but do develop small lesions, which suggests that a reduced level of IL-1ra is insufficient to fully control inflammation in arteries. Our results demonstrate a surprisingly specific role for IL-1ra in the control of spontaneous inflammation in constitutively stressed artery walls, suggesting that expression of IL-1 is likely to have a significant role in signaling artery wall damage.
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影响因子：
37.8
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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