In patients with acute decompensatedheart failure and chronicheart failure, furin activity is increased due to myocardial stress,which contributes to the elevated levels of BNP to compensate forcardiac function.39 Consistently, severalfurin substrates have been shown to contribute to the pathogenesisof heart failure (Figure 5), including inflammatory (TNF-α), remodeling/fibrosis(TGF-β1 and MMP2), and hypertrophic (soluble PRR-mediated ATII, BNP, and ET-1) factors, supporting the role of furin in this setting.53,55,155−157. The gene discussed is TGFB1; the disease is heart failure.