P727Nucleotide-binding oligomerization domain-containing protein 1-signaling is upregulated in hearts from type 2 diabetic mice

Introduction: Type 2 diabetes is a complex pathology that involves deregulated lipid metabolism, insulin resistance together with a chronic inflammatory state. Nucleotide-binding oligomerization domain-containing protein (NOD) 1 is an innate immune system receptor that can participate in the pathogenesis of diabetes in hepatic and adipose tissues. Objetive: The aim of this study was to determine the role of NOD1 in the cardiac inflammatory damage linked to diabetes mellitus. Design. We determined NOD1-pathway activation in cardiac tissue from three mice models harbouring metabolic complications: type 1 diabetic mice, type 2 diabetic mice (db) and mice fed with high fat diet. Results: Only cardiac tissue obtained from db mice showed a significant increase in NOD1 levels that was associated with NF-kB and apoptotic pathways upregulation. On a cellular level, both cardiomyocytes isolated from db mice and HL-1 cardiomyocytes exposed to elevated concentrations of glucose plus palmitate displayed an over-expression of NOD1 as well as NF-kB activation and apoptotic events. This NLR up-regulation was accompanied of a rise in the caspase-3 levels. Conclusions: Our results provide the first time evidence of a role for NOD1 in the increased inflammatory environment related to experimental diabetic cardiac disease.