RGD Reference Report - NOD1 activation induces cardiac dysfunction and modulates cardiac fibrosis and cardiomyocyte apoptosis. - Rat Genome Database

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NOD1 activation induces cardiac dysfunction and modulates cardiac fibrosis and cardiomyocyte apoptosis.

Authors: Fernandez-Velasco, M  Prieto, P  Terron, V  Benito, G  Flores, JM  Delgado, C  Zaragoza, C  Lavin, B  Gomez-Parrizas, M  Lopez-Collazo, E  Martin-Sanz, P  Bosca, L 
Citation: Fernandez-Velasco M, etal., PLoS One. 2012;7(9):e45260. doi: 10.1371/journal.pone.0045260. Epub 2012 Sep 18.
RGD ID: 9831166
Pubmed: PMID:23028889   (View Abstract at PubMed)
PMCID: PMC3445482   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0045260   (Journal Full-text)

The innate immune system is responsible for the initial response of an organism to potentially harmful stressors, pathogens or tissue injury, and accordingly plays an essential role in the pathogenesis of many inflammatory processes, including some cardiovascular diseases. Toll like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors (NLRs) are pattern recognition receptors that play an important role in the induction of innate immune and inflammatory responses. There is a line of evidence supporting that activation of TLRs contributes to the development and progression of cardiovascular diseases but less is known regarding the role of NLRs. Here we demonstrate the presence of the NLR member NOD1 (nucleotide-binding oligomerization domain containing 1) in the murine heart. Activation of NOD1 with the specific agonist C12-iEDAP, but not with the inactive analogue iE-Lys, induces a time- and dose-dependent cardiac dysfunction that occurs concomitantly with cardiac fibrosis and apoptosis. The administration of iEDAP promotes the activation of the NF-kappaB and TGF-beta pathways and induces apoptosis in whole hearts. At the cellular level, both native cardiomyocytes and cardiac fibroblasts expressed NOD1. The NLR activation in cardiomyocytes was associated with NF-kappaB activation and induction of apoptosis. NOD1 stimulation in fibroblasts was linked to NF-kappaB activation and to increased expression of pro-fibrotic mediators. The down-regulation of NOD1 by specific siRNAs blunted the effect of iEDAP on the pro-fibrotic TGF-beta pathway and cell apoptosis. In conclusion, our report uncovers a new pro-inflammatory target that is expressed in the heart, NOD1. The specific activation of this NLR induces cardiac dysfunction and modulates cardiac fibrosis and cardiomyocyte apoptosis, pathological processes involved in several cardiac diseases such as heart failure.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NOD1HumanCardiac Fibrosis  ISONod1 (Mus musculus) RGD 
Nod1MouseCardiac Fibrosis  IDA  RGD 
Nod1RatCardiac Fibrosis  ISONod1 (Mus musculus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nod1Ratpositive regulation of apoptotic process  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nod1  (nucleotide-binding oligomerization domain containing 1)

Genes (Mus musculus)
Nod1  (nucleotide-binding oligomerization domain containing 1)

Genes (Homo sapiens)
NOD1  (nucleotide binding oligomerization domain containing 1)


Additional Information