title: NOD2 contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and inflammation.
abstract: OBJECTIVE
  Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an intracellular pattern recognition receptor, which plays an important role in the innate immunity and inflammation. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. In this study, we sought to determine the role of NOD2 on cardiac I/R injury.
  
  
  METHODS
  Mice were induced 30min ischemia followed by 24h of reperfusion. Histological examinations were performed on heart sections with Evans blue and triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, immunohistochemistry and immunofluorescence staining. The messenger RNA (mRNA) expression and protein levels were detected by real-time polymerase chain reaction (RT-PCR) and western blot analysis respectively.
  
  
  RESULTS
  I/R injury markedly upregulated NOD2 expression in heart tissue. Treatment of WT mice with NOD2 ligand (MDP) significantly increased infarct size, the number of apoptotic cells and inflammatory cells, as compared with wild-type mice after I/R injury. Furthermore, MDP enhanced I/R-induced cardiomyocyte apoptosis and inflammation in vitro, and these effects were attenuated by NOD2-siRNA. The mechanism of NOD2 on cardiac I/R injury is partly associated with JNK, p38MAPK and NF-κB signaling pathways.
  
  
  CONCLUSIONS
  NOD2 aggravates myocardial I/R injury by inducing cardiomyocyte apoptosis and inflammation through JNK, p38MAPK and NF-κB signaling pathways. This study provides insight into better understanding the molecular mechanism of NOD2, which may be served as a potential target for the treatment of myocardial I/R injury.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Physiology and Physiopathology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Liu
authors.affiliation: Department of Physiology and Physiopathology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Vascular Surgery, Peking University First Hospital, Beijing, China.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Guo
authors.affiliation: Department of Physiology and Physiopathology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Department of Physiology and Physiopathology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Tian
authors.affiliation: Department of Physiology and Physiopathology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
authors.affiliation: Department of Physiology and Physiopathology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. Electronic address: whxdy112@ccmu.edu.cn.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse
keywords: Apoptosis; Inflammation; Ischemia/reperfusion injury; NOD2