Specific NLRP3 Inhibition Protects Against Diabetes-Associated Atherosclerosis

Low-grade persistent inflammation is a feature of diabetes-driven vascular complications, in particular activation of the NLRP3-inflammasome to trigger the maturation and release of the inflammatory cytokine interleukin-1β (IL-1β). We investigated whether inhibiting the NLRP3-inflammasome, through the use of the specific small-molecule NLRP3 inhibitor, MCC950, could reduce inflammation, improve vascular function and protect against diabetes-associated atherosclerosis in the streptozotocin (STZ)-induced diabetic Apolipoprotein knockout (ApoE-/-) mouse. Diabetes led to a ∼4-fold increase in atherosclerotic lesions throughout the aorta, which were significantly attenuated with MCC950 (P