NOD2 contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and inflammation

Abstract

AimsNucleotide-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. Main methodsMice 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. Key findingsI/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. SignificanceNOD2 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.