The myocardial extracellular matrix (ECM), which preserves the geometry and integrity of the myocardium, is a dynamic structure whose component
proteins are maintained by a finely controlled homeostatic balance between deposition and degradation. One of the key targets in cardiology is the elucidation of the molecular mechanisms which mediate pathological remodelling of this matrix causing the transition from compensatory
hypertrophy to congestive decompensated
heart failure. In response to injury or increased workload, cardiac remodelling including myocyte
hypertrophy, develops as the heart attempts to compensate for increased wall stresses. Persistence of these stresses over extended time periods leads to disruption of ECM homeostasis resulting in irreversible maladaptive cardiac remodelling, ventricular dilatation and finally
heart failure. ECM remodelling is regulated by the
matrix metalloproteinases (
MMPs) and their endogenous inhibitors (TIMPs). Clinical studies and experimental models of
cardiac disease states have reported alterations in the balance between the
MMPs and TIMPs in the failing heart and crucially at intermediate time points in the progression to failure. This article reviews the recent clinical, genetic and experimental approaches employed to compare ECM,
MMP and TIMP profiles in healthy, compensated and failing hearts and identifies common themes in the perturbation of ECM homeostasis in the transition to
heart failure.