NOD1 receptor is upregulated in diabetic human and murine myocardium

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 oligomerization domain 1), and the pathogenesis of diabetes in monocytes and hepatic and adipose tissues. The aim of this study was to assess the role of NOD1 in the progression of diabetic cardiomyopathy. We measured NOD1 protein in cardiac tissue from type 2 diabetic mice (db). Heart and isolated cardiomyocytes from db mice revealed a significant increase in NOD1, together with an upregulation of NF-kB and increased apoptosis. Heart tissue also exhibited an enhanced expression of proinflammatory cytokines. Selective NOD1 activation with C12-iE-DAP resulted in increased NF-kB 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-kB 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 normoglycemic individuals without cardiovascular histories (NH). We found that NOD1 was expressed in both NH and T2DMH; however, NOD1 expression was significantly pronounced in T2DMH. Furthermore, both the proinflammatory cytokine TNF-α and the apoptosis mediator caspase-3 were...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research