Extracellular matrix profiles in the progression to heart failure: European Young Physiologists Symposium Keynote Lecture-Bratislava 2007

H. K. Graham, M. Horn, A. W. Trafford

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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. © 2008 The Authors.
    Original languageEnglish
    Pages (from-to)3-21
    Number of pages18
    JournalActa Physiologica
    Volume194
    Issue number1
    DOIs
    Publication statusPublished - Sept 2008

    Keywords

    • Collagen
    • Extracellular matrix
    • Heart failure
    • Hypertrophy
    • Matrix metalloproteinase
    • Remodelling

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