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The presence and extent of myocardial fibrosis are key determinants of response to treatment and prognosis in a number of cardiac conditions. Until recently, myocardial fibrosis could only be detected ante mortem by endomyocardial biopsy, which is associated with procedural risk and sampling error. The development of novel cardiac imaging techniques and serum assays now permits the accurate detection and quantification of myocardial fibrosis. These have yielded new insights into disease prognosis and response to treatment.
Pathogenesis of myocardial fibrosis
Myocardial fibrosis develops in response to a cardiac insult, which may include ischaemia, pressure or volume overload, viral infection, or genetically mediated injury as in hypertrophic cardiomyopathy. Net collagen deposition results from an imbalance of its synthesis relative to degradation. A number of enzymes have been identified as potential mediators of myocardial extracellular matrix turnover. The matrix metalloproteinases (MMPs) are a family of at least 20 calcium dependent endopeptidases that digest interstitial constituents. The various MMPs have different substrates—MMP-1 and -13 are collagenases and MMP-2 and -9 gelatinases. Left ventricular (LV) myocardial MMP activity in idiopathic dilated cardiomyopathy and ischaemic cardiomyopathy has been shown to be greater than in normal hearts.1 Abolition of MMP-9 synthesis has been associated with reduced myocardial fibrosis and improved LV function in a rodent model of pressure overload.w1 The tissue inhibitors of matrix metalloproteinase (TIMPs) are a family of four proteins that bind to and inhibit the effects of MMPs (figure 1). TIMP-1 expression is reduced in explanted hearts from patients with both ischaemic and non-ischaemic cardiomyopathy.w2
Regardless of the aetiology and/or molecular cascade resulting in collagen deposition, the presence …
Funding Dr Leong is supported by a Medical Postgraduate Scholarship funded jointly by the National Health and Medical Research Council of Australia and the National Heart Foundation of Australia.
Competing interests In compliance with EBAC/EACCME guidelines, all authors participating in Education in Heart have disclosed potential conflicts of interest that might cause a bias in the article. The authors have no competing interests.
Provenance and peer review Commissioned; not externally peer reviewed.