Enhanced NF-κB Activity Impairs Vascular Function Through PARP-1–, SP-1–, and COX-2–Dependent Mechanisms in Type 2 Diabetes

• DOI: 10.2337/db12-1374
• Publication Date: 2013-01-25T03:52:20Z
• Authors: Modar Kassan; Soo-Kyoung Choi; Maria Galán; Alexander Bishop; Kazuo Umezawa; Mohamed Trebak; Souad Belmadani; Khalid Matrougui
• Keywords: PARP inhibitor; IκB kinase; Mesenteric arteries; Endothelial Dysfunction

Type 2 diabetes (T2D) is associated with vascular dysfunction. We hypothesized that increased nuclear factor-κB (NF-κB) signaling contributes to dysfunction in T2D. treated type diabetic (db(-)/db(-)) and control (db(-)/db(+)) mice two NF-κB inhibitors (6 mg/kg dehydroxymethylepoxyquinomicin twice a week 500 μg/kg/day IKK-NBD peptide) for 4 weeks. Pressure-induced myogenic tone was significantly potentiated, while endothelium-dependent relaxation (EDR) impaired small coronary arterioles mesenteric resistance artery from compared controls. Interestingly, had reduced potentiation improved EDR. Importantly, function also rescued db(-)/db(-p50NF-κB-/-) db(-)/db(-PARP-1-/-) double knockout db(-)/db(-) mice. Additionally, the acute vitro downregulation of NF-κB-p65 using p65NF-κB short hairpin RNA lentivirus arteries function. The inhibition did not affect blood glucose level or body weight. levels Sp-1 eNOS phosphorylation were decreased, phosphorylation, cleaved poly(ADP-ribose) polymerase (PARP)-1, cyclooxygenase (COX)-2 expression mice, which restored after In current study, we provided evidence enhanced activity impairs by PARP-1-, Sp-1-, COX-2-dependent mechanisms male Therefore, could be potential target overcome diabetes-induced