RT Journal Article
T1 NOD1 Activation Induces Cardiac Dysfunction and Modulates Cardiac Fibrosis and Cardiomyocyte Apoptosis
A1 Fernández-Velasco, María
A1 Prieto, Patricia
A1 Terrón, Verónica
A1 Benito, Gemma
A1 Flores Landeira, Juana María
A1 Delgado, Carmen
A1 Zaragoza, Carlos
A1 Lavín Plaza, Begoña
A1 Gómez-Parrizas, Mónica
A1 López-Collazo, Eduardo
A1 Martín Sanz, Paloma
A1 Bosca Gomar, Lisardo
AB 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-κB and TGF-β 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-κB activation and induction of apoptosis. NOD1 stimulation in fibroblasts was linked to NF-κB 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-β 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.
PB Public Library of Science
SN 1932-6203
YR 2012
FD 2012
LK https://hdl.handle.net/20.500.14352/96479
UL https://hdl.handle.net/20.500.14352/96479
LA eng
NO Fernández-Velasco, María, et al. «NOD1 Activation Induces Cardiac Dysfunction and Modulates Cardiac Fibrosis and Cardiomyocyte Apoptosis». PLoS ONE, editado por Tianqing Peng, vol. 7, n.o 9, septiembre de 2012, p. e45260. https://doi.org/10.1371/journal.pone.0045260.
NO Instituto de Salud Carlos III
NO Ministerio de Ciencia e Innovación (España)
NO Fondo de Investigacion Sanitario-Red Cardiovascular
DS Docta Complutense
RD 9 abr 2025