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Intracellular Matrix Remodeling and Cardiac Function in Ischemia–Reperfusion Injury

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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

The effects of ischemia on animal and human myocardium have been extensively studied during the last four decades. Myocardial ischemia followed by subsequent reperfusion can cause profound damage to cardiac myocytes through enhanced oxidative stress and intracellular Ca2+ overload. Ischemia–reperfusion injury leads to structural and functional remodeling of multiple intracellular matrix components in the cardiac myocyte. The intracellular matrix of cardiac myocytes includes major cytosolic components that include the cytoskeleton, contractile myofibrils, and subcellular organelles such as mitochondria, sarcoplasmic reticulum, and the nucleus. There are several proteolytic pathways inside the cell which may participate in cell injury and/or cell repair upon reperfusion of ischemic heart muscle. These include matrix metalloproteinases, calpains, lysosomal proteases, and the proteasome system, which are a major focus of research in ischemia–reperfusion injury. The discovery of intramyocyte matrix metalloproteinase-2 (MMP-2) and biologically relevant protein substrates of it in the intracellular matrix has shaped a new paradigm of the pathophysiological role of MMP-2 during myocardial ischemia–reperfusion injury. Emerging evidence indicates that oxidative stress can efficiently activate intracellular MMP-2 which rapidly mediates intracellular matrix remodeling of injured myocytes. This chapter will focus on the structural and functional remodeling of the intracellular matrix including the sarcomere, cytoskeleton, mitochondria, and nucleus, by proteolytic and other processes, in the context of ischemia–reperfusion (I/R) injury, with a particular emphasis on the rapidly expanding knowledge of the role of intracellular MMP-2.

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Acknowledgments

We thank Dawne Colwell for her professional assistance in preparing the illustrations. Research in the Schulz laboratory is supported by the Canadian Institutes of Health Research (MOP-77526 and MOP-66953). MAM received a graduate trainee award from Alberta Innovates—Health Solutions. ALBJF is supported by a fellowship award from Alberta Innovates—Health Solutions and an incentive award from the Mazankowski Alberta Heart Institute.

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Authors and Affiliations

  1. Departments of Pediatrics and Pharmacology, Cardiovascular Research Centre, 4–62 HMRC, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada, T6G 2S2

    Xiaohu Fan, Mohammad A. M. Ali, Bryan G. Hughes, Anna Laura B. Jacob-Ferreira & Richard Schulz

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  1. Xiaohu Fan
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  2. Mohammad A. M. Ali
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  4. Anna Laura B. Jacob-Ferreira
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  5. Richard Schulz
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Correspondence to Richard Schulz .

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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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Fan, X., Ali, M.A.M., Hughes, B.G., Jacob-Ferreira, A.L.B., Schulz, R. (2013). Intracellular Matrix Remodeling and Cardiac Function in Ischemia–Reperfusion Injury. 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_26

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