TGFB1 and heart failure: However, direct inhibition of TGF-β-signalling has proved to have ambiguous effects in rats exposed to pressure overload due to detrimental effects on wound healing.68 Therefore, approaches to inhibit the detrimental actions of TGF-β without interfering with its physiological roles are warranted.69 The findings that ADAMTS4 is up-regulated in heart failure and that it cleaves EDA-fibronectin, which is an ECM component mainly seen in diseased tissue, strengthen the idea that ADAMTS4 should be a specific target in TGF-β modulation and anti-fibrotic treatment in heart disease.