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The Role of Growth Differentiation Factor 5 in Cardiac Repair Post-Myocardial Infarction

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Cardiac Remodeling

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 5))

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Abstract

Progressive post-myocardial infarction (MI) remodelling of the heart is mediated by processes that include apoptosis, proliferation, fibrosis and hypertrophy. The regulation of pathways leading to these events can be mediated by diverse factors present in specific spatiotemporal expression patterns post-MI. The growth differentiation factors (GDFs) which are closely related to the bone morphogenetic protein (BMP) family of growth factors regulate diverse processes in many tissues including the heart. The GDF/BMPs regulate a cascade of intracellular signalling molecules to affect gene regulation in target cells. GDF/BMP signal transduction is mediated by specific receptor heteromer activation, extracellular inhibition and intracellular regulation of downstream signalling. Despite roles in cardiac development, the role of specific GDF/BMPs in post-MI processes is not well known. While GDF-5 does not appear to be involved in cardiac development, it is involved in a variety of processes mediating both acute and chronic remodelling post-MI. As a function of specific heteromeric receptor activation and resultant downstream signalling cascades, GDF-5 impacts specific pathways differentially in cardiomyocytes, cardiac fibroblasts and endothelial and vascular smooth muscle cells. GDF-5 spares cardiomyocyte apoptosis via a SMAD1/5/8-SMAD4-Bcl/Bcl-xL-mediated process, increases vascularity post-MI and decreases p38-mediated collagen production post-MI. Thus, a single growth factor is able to exert a multitude of cardioactive effects post-MI, which together represent a potential therapeutic target.

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Authors and Affiliations

  1. Toronto General Hospital Research Institute, University Health Network, 200 Elizabeth St, MaRS 3-909, Toronto, ON, Canada, M5G 2C4

    Eric A. Shikatani & Mansoor Husain M.D.

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  1. Eric A. Shikatani
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  2. Mansoor Husain M.D.
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Correspondence to Mansoor Husain M.D. .

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  1. Walter MacKenzie Health Sciences Centre, Division of Cardiology, University of Alberta, 8440-112 Street, Edmonton, T6G 2B7, Alberta, Canada

    Bodh I. Jugdutt

  2. St. Boniface General Hospital Research C, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

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Shikatani, E.A., Husain, M. (2013). The Role of Growth Differentiation Factor 5 in Cardiac Repair Post-Myocardial Infarction. In: Jugdutt, B., Dhalla, N. (eds) Cardiac Remodeling. Advances in Biochemistry in Health and Disease, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5930-9_21

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