Type 2 diabetes has a complex pathology that involves a chronic inflammatory state. Emerging evidence suggests a link between the innate immune system receptor NOD1 (nucleotide-binding and oligomerization domain 1) and the pathogenesis of diabetes, in monocytes and hepatic and adipose tissues. The aim of the present study was to assess the role of NOD1 in the progression of diabetic cardiomyopathy. We have measured NOD1 protein in cardiac tissue from Type 2 diabetic (db) mice. Heart and isolated cardiomyocytes from db mice revealed a significant increase in NOD1, together with an up-regulation of nuclear factor κB (NF-κB) and increased apoptosis. Heart tissue also exhibited an enhanced expression of pro-inflammatory cytokines. Selective NOD1 activation with C12-γ-D-glutamyl-m-diaminopimelic acid (iEDAP) resulted in an increased NF-κB activation and apoptosis, demonstrating the involvement of NOD1 both in wild-type and db mice. Moreover, HL-1 cardiomyocytes exposed to elevated concentrations of glucose plus palmitate displayed an enhanced NF-κB activity and apoptotic profile, which was prevented by silencing of NOD1 expression. To address this issue in human pathology, NOD1 expression was evaluated in myocardium obtained from patients with Type 2 diabetes (T2DMH) and from normoglycaemic individuals without cardiovascular histories (NH). We have found that NOD1 was expressed in both NH and T2DMH; however, NOD1 expression was significantly pronounced in T2DMH. Furthermore, both the pro-inflammatory cytokine tumour necrosis factor α (TNF-α) and the apoptosis mediator caspase-3 were up-regulated in T2DMH samples. Taken together, our results define an active role for NOD1 in the heightened inflammatory environment associated with both experimental and human diabetic cardiac disease.
NOD1 receptor is up-regulated in diabetic human and murine myocardium
Patricia Prieto, María Teresa Vallejo-Cremades, Gemma Benito, Pilar González-Peramato, Daniel Francés, Noelia Agra, Verónica Terrón, Silvia Gónzalez-Ramos, Carmen Delgado, Mariano Ruiz-Gayo, Ivette Pacheco, Juan P. Velasco-Martín, Javier Regadera, Paloma Martín-Sanz, Eduardo López-Collazo, Lisardo Boscá, María Fernández-Velasco; NOD1 receptor is up-regulated in diabetic human and murine myocardium. Clin Sci (Lond) 1 December 2014; 127 (12): 665–677. doi: https://doi.org/10.1042/CS20140180
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