| First Author | Monnerat G | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13344 | PubMed ID | 27882934 |
| Mgi Jnum | J:243066 | Mgi Id | MGI:5907558 |
| Doi | 10.1038/ncomms13344 | Citation | Monnerat G, et al. (2016) Macrophage-dependent IL-1beta production induces cardiac arrhythmias in diabetic mice. Nat Commun 7:13344 |
| abstractText | Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1beta in DM mice. IL-1beta causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity. IL-1beta-induced spontaneous contractile events are associated with CaMKII oxidation and phosphorylation. We further show that DM-induced arrhythmias can be successfully treated by inhibiting the IL-1beta axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1beta as an inflammatory connection between metabolic dysfunction and arrhythmias in DM. |
