NOX and inflammation in the vascular adventitia.
NOX and inflammation in the vascular adventitia.
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DOI：
10.1016/j.freeradbiomed.2009.07.022
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发表时间：
2009-11-01
影响因子：
7.4
通讯作者：
Pagano, Patrick J.
中科院分区：
文献类型：
--
作者：
Csanyi, Gabor;Taylor, W. Robert;Pagano, Patrick J.
关键词：
传统上认为血管炎症是在管腔表面引发的，并通过中质进展至外膜层。然而，近年来出现的证据表明，血管外膜在多种心血管疾病的早期就被激活，并且在血管炎症的发生和进展中发挥着重要作用。外膜成纤维细胞已被证明会产生大量 NAD(P)H 氧化酶衍生的活性氧 (ROS) 以应对血管损伤。此外，与成纤维细胞增殖和迁移有关的炎症细胞因子、脂质和各种激素会导致炎症细胞募集到外膜层并损害内皮依赖性松弛。在血管疾病发展的早期，有明确的证据表明血管滋养管向更致密的方向发展，该血管向日益缺氧和营养缺乏的介质输送氧气和营养物质。这种扩张的血管化似乎增强了炎症细胞向外膜和外中膜的输送。因此，外膜成纤维细胞和炎症细胞衍生的 ROS 的组合预计将协同它们对外膜实质细胞的局部作用，导致进一步的细胞因子释放和外膜 ROS 产生的前馈传播。事实上，我们实验室和其他实验室的数据表明，外膜衍生的 ROS 在内侧平滑肌细胞肥大和新内膜增生中具有更广泛的旁分泌正反馈作用。超氧阴离子代谢物过氧化氢可能是负责跨血管壁的外膜衍生旁分泌信号传导的候选者，它高度稳定，具有细胞渗透性，并且能够激活平滑肌细胞中的下游信号传导机制。这导致平滑肌细胞的表型调节。这篇综述探讨了外膜 NAD(P)H 氧化酶衍生的 ROS 在促进血管炎症方面的非传统血管周围优势的作用，并将讨论外膜 NAD(P)H 氧化酶衍生的 ROS 如何成为血管重塑和功能障碍的催化剂。
Vascular inflammation has traditionally been thought to be initiated at the luminal surface and progress through the media toward the adventitial layer. In recent years, however, evidence has emerged suggesting that the vascular adventitia is activated early in a variety of cardiovascular diseases and that it plays an important role in the initiation and progression of vascular inflammation. Adventitial fibroblasts have been shown to produce substantial amounts of NAD(P)H oxidase-derived reactive oxygen species (ROS) in response to vascular injury. Additionally, inflammatory cytokines, lipids and various hormones, implicated in fibroblast proliferation and migration, lead to recruitment of inflammatory cells to the adventitial layer and impairment of endothelium-dependent relaxation. Early in the development of vascular disease, there is clear evidence for progression toward a denser vasa vasorum which delivers oxygen and nutrients to an increasingly hypoxic and nutrient-deficient media. This expanded vascularization appears to provide enhanced delivery of inflammatory cells to the adventitia and outer media. A combined adventitial fibroblast and inflammatory cell-derived ROS therefore is expected to synergize their local effect on adventitial parenchymal cells leading to further cytokine release and a feed-forward propagation of adventitial ROS production. In fact, data from our laboratory and others suggest a broader paracrine positive feedback role for adventitia-derived ROS in medial smooth muscle cell hypertrophy and neointimal hyperplasia. A likely candidate responsible for the adventitia-derived paracrine signaling across the vessel wall is the superoxide anion metabolite hydrogen peroxide, which is highly stable, cell-permeant and capable of activating downstream signaling mechanisms in smooth muscle cells. This leads to phenotypic modulation of smooth muscle cells. This review addresses the role of adventitial NAD(P)H oxidase-derived ROS from a non-traditional, perivascular vantage of promoting vascular inflammation and will discuss how ROS derived from adventitial NAD(P)H oxidases may be a catalyst for vascular remodeling and dysfunction.
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影响因子：
20.1
作者：
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