title: NOD2 deficiency protects against cardiac remodeling after myocardial infarction in mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Fengli
authors.initials: F
authors.lastname: Li
authors.forename: Yongli
authors.initials: Y
authors.lastname: Chu
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ziying
authors.initials: Z
authors.lastname: Wang
authors.forename: Xinbing
authors.initials: X
authors.lastname: Wei
authors.forename: Wencheng
authors.initials: W
authors.lastname: Jian
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Yi
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053473:Nod2 Signaling Adaptor Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D016207:Cytokines; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020780:Matrix Metalloproteinase 9