Signalling pathways linking cysteine cathepsins to adverse cardiac remodelling

Adverse cardiac remodelling clinically manifests as deleterious changes to heart architecture (size, mass and geometry) and function. These changes, which include alterations to ventricular wall thickness, chamber dilation and poor contractility, are important because they progressively drive patients with cardiac disease towards heart failure and are associated with poor prognosis. Cysteine cathepsins contribute to key signalling pathways involved in adverse cardiac remodelling including synthesis and degradation of the cardiac extracellular matrix (ECM), cardiomyocyte hypertrophy, impaired cardiomyocyte contractility and apoptosis. In this review, we highlight the role of cathepsins in these signalling pathways as well as their translational potential as therapeutic targets in cardiac disease.