title: Activation of NOD1 by DAP contributes to myocardial ischemia/reperfusion injury via multiple signaling pathways.
abstract: NOD1 is a member of nucleotide-binding oligomerization domain-like receptors family that participates in many inflammatory processes. Previous studies demonstrated that NOD1 plays an important role in inflammatory cardiovascular diseases. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. The present study investigate whether NOD1 is involved in the pathogenesis of mouse myocardial I/R injury and the underlying mechanisms. Administration of NOD1 ligand (DAP) significantly enhanced myocardial I/R injury, as demonstrated by increased infarct size, the number of TUNEL-positive nuclei, caspase-3 activity, the infiltration of Mac-2- and IL-6-positive cells as compared with untreated heart or cardiomyocytes after I/R injury. In contrast, knockdown of NOD1 by siRNA markedly attenuated mimetic I/R induced cardiomyocyte apoptosis in vitro, indicating that NOD1 enhanced myocardial I/R injury partially through direct heart effects. These effects were partially associated with activation of JNK, p38 MAPK and NF-κB signaling pathways. Taken together, these results provide the first evidence that activation of intracellular sensor NOD1 enhances myocardial I/R injury and may provide novel therapeutic target for ameliorating the ischemic heart diseases.
authors.affiliation: Department of Physiology, Pathology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing, 100069, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Song
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Cui
authors.initials: C
authors.lastname: Tian
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Yu
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D003960:Diaminopimelic Acid / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000378:metabolism / Q000601:surgery*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D003960:Diaminopimelic Acid; D048670:MAP Kinase Kinase 4