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Collagen Processing and its Role in Fibrosis

  • Christopher A. McCullochEmail author
  • Nuno M. Coelho
Chapter
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 13)

Abstract

In several diseases involving the heart such as pressure overload, diabetic cardiomyopathy or myocardial infarction, fibrosis is a common disorder of myocardial extracellular matrix structure and function. The clinical significance of fibrosis is that accumulation of disorganized fibrillar collagen in the cardiac interstitium can inhibit diastolic and systolic function. Fibrosis is mediated by several different cellular and extracellular processes including disruptions of fibroblast differentiation, perturbations of post-translational processing and assembly of matrix molecules, and inappropriately organized matrix degradation by proteases and intracellular digestion. The enlargement of transformed fibroblast and myofibroblast populations in the diseased cardiac interstitium plays a critical role in the disorganized matrix remodeling that occurs after pressure overload or diabetes because these cells do not process and remodel interstitial collagen in a physiological fashion. New data that have examined the regulation of pro-collagen processing by molecules such as pro-collagen C-endopeptidase enhancer and modulation of collagen assembly by the secreted protein acidic and rich in cysteine, have suggested novel therapeutic targets for ameliorating cardiac fibrosis. Further, studies of transmembrane matrix metalloproteinases, such as MT-1, indicate the remarkable breadth of function and complexity of the matrix proteolytic family since MT-1 can break down the matrix and is also important in mediating collagen degradation by phagocytosis. Our growing recognition that the myocardial matrix is highly dynamic and comprises a wide range of matricellular and non-structural proteins and proteases in addition to well-defined structural proteins, suggests new approaches for myocardial fibrosis in a spectrum of cardiac diseases.

Keywords

Collagen Phagocytosis Matrix Turnover Proteases Assembly Matrix metalloproteinases 

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Matrix Dynamics GroupUniversity of TorontoTorontoCanada

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