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Role of SPARC in Cardiac Extracellular Matrix Remodeling After 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

Research of the last decades has established that the cardiac extracellular matrix (ECM) is not a static but rather a dynamic environment in which the cellular and acellular components of the heart communicate and function. Remodeling after myocardial infarction (MI) associates with cardiac rupture or maladaptive left ventricular remodeling resulting in cardiac dilatation, dysfunction, and increased mortality. The dynamic synthesis and breakdown of the cardiac ECM-related proteins and the formation of a well-organized collagen scar play a major role in the structural and functional recovery of the infarcted heart. Secreted protein acidic and rich in cysteine (SPARC) is a prototypical collagen-binding matricellular protein and has been proven to coordinate procollagen processing and facilitate collagen fibril assembly in the pericellular environment. SPARC is vastly upregulated in response to cardiac stress, including MI. The lack of SPARC resulted in a fourfold higher incidence of mortality following MI, due to increased rates of cardiac rupture and heart failure, which was associated with a highly impaired and immature collagen scar. In contrast, adenoviral overexpression of SPARC improved collagen maturation in the infarct scar, associated with increased transforming growth factor (TGF)-β signaling, and prevented cardiac dilatation and dysfunction after MI. Therefore, this chapter focuses on (1) the role of SPARC during cardiac remodeling after MI and (2) the potential mechanisms involved in SPARC-mediated extracellular ­post-synthetic procollagen processing in the infarcted heart.

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Acknowledgments

S.H. received a Vidi grant from the Netherlands Organization for Scientific Research (NWO, 91796338) and research grants from the Netherlands Heart Foundation (2008B011), Fund of Scientific Research Flanders (FWO-Vlaanderen, G074009N), European Union, FP7-HEALTH-2010, MEDIA, large-scale integrating project, and European Union, FP7-HEALTH-2011, EU-Mascara. D.V. is supported by a fellowship of the Fund of Scientific Research Flanders (FWO-Vlaanderen, Belgium, 1208910N).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, 240 Albert Sabin Way, MLC 7020, Cincinnati, OH, USA

    Davy Vanhoutte Ph.D.

  2. Department of Cardiovascular Sciences, K.U. Leuven, Leuven, Belgium

    Davy Vanhoutte Ph.D. & Stephane Heymans

  3. Center for Heart Failure Research, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Stephane Heymans

Authors
  1. Davy Vanhoutte Ph.D.
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  2. Stephane Heymans
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Correspondence to Davy Vanhoutte Ph.D. .

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Editors and Affiliations

  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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Vanhoutte, D., Heymans, S. (2013). Role of SPARC in Cardiac Extracellular Matrix Remodeling After 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_24

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