Novel model of inflammatory neointima formation reveals a potential role of myeloperoxidase in neointimal hyperplasia.
Novel model of inflammatory neointima formation reveals a potential role of myeloperoxidase in neointimal hyperplasia.
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炎症性新内膜形成的新模型揭示了髓过氧化物酶在新内膜增生中的潜在作用。
DOI：
10.1152/ajpheart.00412.2006
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Zhang,Chunxiang
中科院分区：
文献类型：
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作者：
Yang,Jian;Cheng,Yunhui;Ji,Ruirui;Zhang,Chunxiang
以新生内膜形成为特征的动脉粥样硬化是一种炎性疾病。然而，没有炎症产物诱导的新生内膜模型来支持炎症在动脉粥样硬化形成中的因果作用。我们以前报道过白细胞源性MPO诱导血管损伤反应，如内皮功能障碍。我们现在检测MPO在炎症性新生内膜形成中的作用。我们将暂时分离的大鼠颈总动脉灌注MPO（200 nM）并孵育1 h。我们发现，虽然MPO本身没有诱导任何新生内膜形成2周后治疗，在其底物，过氧化氢的存在下，MPO能够引起新生内膜增生。我们进一步证实MPO诱导的新生内膜增生是由其产物次氯酸（HOCl）介导的。HOCl引起内膜和中膜细胞凋亡，随后引起血管增殖反应，并导致异源细胞群的新生内膜形成。HOCl处理血管的组织学和功能特征与动脉粥样硬化病变相似。据我们所知，这是第一次直接在体内证实炎症级联反应产物诱导的新生内膜形成。结果提示，MPO可能是病理性新生内膜生长的介质。这种新的新生内膜模型可能有助于研究炎症和动脉粥样硬化。
Atherosclerosis, which is characterized by neointima formation, is an inflammatory disease. However, there is no inflammatory product-elicited neointimal model to support the causal role of inflammation in atherogenesis. We reported previously that leukocyte-derived MPO induces vascular injury responses such as endothelial dysfunction. We now test the role of MPO in inflammatory neointima formation. We infused temporarily isolated rat common carotid arteries with MPO (200 nM) and incubated for 1 h. We found that although MPO itself did not induce any neointima formation 2 wk after treatment, in the presence of its substrate, hydrogen peroxide, MPO was able to elicit neointimal hyperplasia. We further confirmed that MPO-induced neointimal hyperplasia is mediated by its product, hypochlorous acid (HOCl). HOCl elicited apoptosis both in intima and media followed by vascular proliferative response and resulted in neointima formation with a heterogeneous cell population. Both histological and functional features of HOCl-treated vessels are similar to those in atherosclerotic lesions. To our knowledge, this is the first direct in vivo demonstration of neointimal formation induced by a product of the inflammatory cascade. The results suggest that MPO may be a mediator for pathological neointima growth. This novel neointimal model could be useful for studying inflammation and atherosclerosis.