Assigning matrix metalloproteinase roles in ischaemic cardiac remodelling

Matrix metalloproteinases (MMPs) and their endogenous inhibitors have been studied in the myocardium for the past 2 decades. An incomplete knowledge base and experimental design issues with inhibitors have hampered attempts at translation, but clinical interest remains high because of strong associations between MMPs and outcomes after myocardial infarction (MI) as well as mechanistic studies showing MMP involvement at multiple stages of the MI wound-healing process. This Review focuses on how our understanding of MMPs has evolved from a one-dimensional early focus on measuring MMP activity, monitoring MMP:inhibitor ratios, and evaluating one MMP–substrate pair to the current use of systems biology approaches to integrate the whole MMP repertoire of roles in the left ventricular response to MI. MMP9 is used as an example MMP to explain these concepts and to provide a template for examining MMPs as mechanistic mediators of cardiac remodelling. Matrix metalloproteinases (MMPs) are a family of 25 enzymes that proteolytically process extracellular matrix and inflammatory proteins, making them highly relevant in ischaemic remodelling after myocardial infarction. In this Review, Lindsey focuses on systems biology approaches to integrate the roles of MMPs in left ventricular remodelling, using MMP9 as an example.