NOD2 Deficiency Protects against Cardiac Remodeling after Myocardial Infarction in Mice
NOD2 Deficiency Protects against Cardiac Remodeling after Myocardial Infarction in Mice
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NOD2 缺乏可防止小鼠心肌梗塞后的心脏重塑
DOI：
10.1159/000356618
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发表时间：
2013-01-01
影响因子：
--
通讯作者：
Yi, Fan
中科院分区：
文献类型：
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作者：
Li, Xiang;Li, Fengli;Yi, Fan
背景/目标：虽然心肌梗死（MI）的发病机制是多因素的，但先天免疫系统激活诱导炎症反应已成为MI的关键病理生理过程。NOD 2是NOD样受体（NOD-like receptor，NLR）家族的成员之一，在先天性免疫应答中发挥重要作用。本研究旨在探讨NOD2在心肌梗死中的作用。方法：通过永久性结扎野生型和NOD2-/-小鼠的左冠状动脉诱导MI，分离心肌成纤维细胞。结果：心肌梗死后NOD2表达明显增加。NOD2缺陷改善MI后心功能不全和重构，通过超声心动图分析证明，降低细胞因子水平，炎性细胞浸润和基质金属蛋白酶-9（MMP-9）活性。在体外实验中，我们进一步发现NOD2激活可诱导心肌成纤维细胞MAPK信号通路的激活、促炎介质的产生和MMP-9的活性。结论：我们的研究表明，NOD2是一个信号转导通路的关键组成部分，连接心脏损伤的炎症和MMP-9活性的恶化。NOD2介导的信号通路的药理学靶点可能为心血管疾病的治疗提供新的途径。
Background/Aims: Although the pathogenesis of myocardial infarction (MI) is multifactorial, activation of innate immune system to induce inflammation has emerged as a key pathophysiological process in MI. NOD2, one member of the NOD-like receptor (NLR) family, plays an important role in the innate immune response. This study was to examine the role of NOD2 during MI. Methods: MI was induced by permanent ligation of the left coronary artery in wild type and NOD2-/- mice and cardiac fibroblasts were isolated. Results: NOD2 expression was significantly increased in myocardium in post-MI mice. NOD2 deficiency improved cardiac dysfunction and remodeling after MI as evidenced by echocardiographic analysis, reduced the levels of cytokines, inflammatory cell infiltration and matrix metalloproteinase-9 (MMP-9) activity. In vitro, we further found that NOD2 activation induced the activation of MAPK signaling pathways, production of proinflammatory mediators and MMP-9 activity in cardiac fibroblasts. Conclusions: Our studies demonstrate that NOD2 is a critical component of a signal transduction pathway that links cardiac injury by exacerbation of inflammation and MMP-9 activity. Pharmacological targeting of NOD2-mediated signaling pathways may provide a novel approach to treatment of cardiovascular diseases.