Cells release dormant TGF-β homodimers that are cleaved by chymases, tryptases, or other proteases enabling the TGF-β molecule to bind its receptor (Central Illustration B, Table 1).43, 44, 45 Moreover, chymases generate angiotensin I from angiotensin II,46,47 most likely leading to the generation of up to 75% of angiotensin II via the chymase pathway during heart failure.48 This evidence concerns the gene TGFB1 and heart failure.