RNLS and heart failure: Several lines of evidence suggest that recombinant renalase substantially mediates non-canonical TGF-β (Smad-independent) pro-fibrotic pathways, in experimentally induced heart and kidney fibrosis (68, 69, 84), including diabetic nephropathy (17), and pressure overload-induced heart failure (21), presuming that if treated with renalase, it results in an appropriate, therefore plausible fibrotic feed-back.