Cardiac fibroblasts account for up to two-thirds of the total number of cells in the normal heart and are responsible for extracellular matrix homoeostasis. In vitro, type I collagen, the predominant myocardial collagen, stimulates proteolytic activation of constitutively secreted proMMP-2 (pro-matrix metalloproteinase-2). This occurs at the cell membrane and requires formation of a ternary complex with MT1-MMP (membrane-type-1 MMP) and TIMP-2 (tissue inhibitor of metalloproteinases-2). Following MI (myocardial infarction), normally quiescent fibroblasts initiate a wound healing response by transforming into a proliferative and invasive myofibroblast phenotype. Deprivation of oxygen to the myocardium is an inevitable consequence of MI; therefore this reparative event occurs under chronically hypoxic conditions. However, species and preparation variations can strongly influence fibroblast behaviour, which is an important consideration when selecting experimental models for provision of clinically useful information.
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November 2007
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Conference Article|
October 25 2007
Hypoxic inhibition of human cardiac fibroblast invasion and MMP-2 activation may impair adaptive myocardial remodelling
M.E. Morley;
M.E. Morley
1Academic Unit of Cardiovascular Medicine, LIGHT (Leeds Institute of Genetics, Health and Therapeutics), University of Leeds, Leeds LS2 9JT, U.K.
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K. Riches;
K. Riches
1Academic Unit of Cardiovascular Medicine, LIGHT (Leeds Institute of Genetics, Health and Therapeutics), University of Leeds, Leeds LS2 9JT, U.K.
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C. Peers;
C. Peers
1Academic Unit of Cardiovascular Medicine, LIGHT (Leeds Institute of Genetics, Health and Therapeutics), University of Leeds, Leeds LS2 9JT, U.K.
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K.E. Porter
K.E. Porter
1
1Academic Unit of Cardiovascular Medicine, LIGHT (Leeds Institute of Genetics, Health and Therapeutics), University of Leeds, Leeds LS2 9JT, U.K.
1To whom correspondence should be addressed, at Institute for Cardiovascular Research, Worsley Building, Clarendon Way, University of Leeds, Leeds LS2 9JT, U.K. (email medkep@leeds.ac.uk).
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Publisher: Portland Press Ltd
Received:
June 15 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (5): 905–907.
Article history
Received:
June 15 2007
Citation
M.E. Morley, K. Riches, C. Peers, K.E. Porter; Hypoxic inhibition of human cardiac fibroblast invasion and MMP-2 activation may impair adaptive myocardial remodelling. Biochem Soc Trans 1 November 2007; 35 (5): 905–907. doi: https://doi.org/10.1042/BST0350905
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