Using the same mouse models, another study also showed that the chymase inhibitor JNJ-18054478 prevented the generation of the mature potent vasoconstrictor endothelin-1 from its precursor form, supporting the notion that intrarenal chymase-dependent ET-1 production contributes to the decline in function and progression to end-stage renal disease in patients with type-2 diabetes [66] (Figure 1). This evidence concerns the gene EDN1 and type 2 diabetes mellitus.