Li Xiang, Li Fengli, Chu Yongli, Wang Xiaojie, Zhang Hongyu, Hu Yanyan, Zhang Yan, Wang Ziying, Wei Xinbing, Jian Wencheng, Zhang Xiumei, Yi Fan
Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
Cell Physiol Biochem. 2013;32(6):1857-66. doi: 10.1159/000356618. Epub 2013 Dec 20.
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.
MI was induced by permanent ligation of the left coronary artery in wild type and NOD2(-/-) mice and cardiac fibroblasts were isolated.
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.
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.
背景/目的：尽管心肌梗死（MI）的发病机制是多因素的，但激活先天免疫系统以诱导炎症已成为MI关键的病理生理过程。NOD样受体（NLR）家族成员之一NOD2在先天免疫反应中起重要作用。本研究旨在探讨NOD2在MI中的作用。
通过永久性结扎野生型和NOD2基因敲除小鼠的左冠状动脉诱导MI，并分离心脏成纤维细胞。
MI后小鼠心肌中NOD2表达显著增加。超声心动图分析表明，NOD2缺乏改善了MI后的心脏功能障碍和重塑，降低了细胞因子水平、炎症细胞浸润和基质金属蛋白酶-9（MMP-9）活性。在体外，我们进一步发现NOD2激活诱导心脏成纤维细胞中MAPK信号通路的激活、促炎介质的产生和MMP-9活性。
我们的研究表明，NOD2是通过炎症加剧和MMP-9活性导致心脏损伤的信号转导途径的关键组成部分。对NOD2介导的信号通路进行药物靶向治疗可能为心血管疾病的治疗提供一种新方法。
