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The extracellular matrix in myocardial injury, repair, and remodeling
Nikolaos G. Frangogiannis
Nikolaos G. Frangogiannis
Published May 1, 2017
Citation Information: J Clin Invest. 2017;127(5):1600-1612. https://doi.org/10.1172/JCI87491.
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Review

The extracellular matrix in myocardial injury, repair, and remodeling

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Abstract

The cardiac extracellular matrix (ECM) not only provides mechanical support, but also transduces essential molecular signals in health and disease. Following myocardial infarction, dynamic ECM changes drive inflammation and repair. Early generation of bioactive matrix fragments activates proinflammatory signaling. The formation of a highly plastic provisional matrix facilitates leukocyte infiltration and activates infarct myofibroblasts. Deposition of matricellular proteins modulates growth factor signaling and contributes to the spatial and temporal regulation of the reparative response. Mechanical stress due to pressure and volume overload and metabolic dysfunction also induce profound changes in ECM composition that contribute to the pathogenesis of heart failure. This manuscript reviews the role of the ECM in cardiac repair and remodeling and discusses matrix-based therapies that may attenuate remodeling while promoting repair and regeneration.

Authors

Nikolaos G. Frangogiannis

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Figure 1

The ECM during the inflammatory phase of cardiac repair.

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The ECM during the inflammatory phase of cardiac repair.
(A) Cardiomyocy...
(A) Cardiomyocyte necrosis is associated with induction and activation of proteases in the infarcted region. Activated proteases cause fragmentation of the native ECM, resulting in release of matrikines, bioactive peptides that activate an inflammatory macrophage phenotype and may also modulate responses of fibroblasts and vascular endothelial cells. The effects of MMPs in the ischemic and infarcted myocardium are not limited to the ECM. MMPs may modulate inflammatory and reparative responses by processing cytokines and chemokines. They may also inhibit chemokine actions by degrading glycosaminoglycan-binding sites and mediate dysfunction by targeting intracellular proteins. Increased vessel permeability in the infarcted region results in extravasation of plasma proteins, such as fibrinogen and fibronectin. Accumulation of these proteins in the infarcted region forms a provisional matrix that serves as a scaffold for infiltrating leukocytes. Fibrin and fibronectin modulate the phenotype of immune and reparative cells through integrin-mediated actions. (B) Fibrinogen/fibrin staining using a peroxidase-based technique (black) illustrates the formation of the provisional fibrin-based matrix network (indicated by arrows) in the infarcted canine myocardium (one hour ischemia followed by seven days reperfusion). Counterstained with eosin. Scale bar: 50 μm. Reproduced with permission from the FASEB Journal (155).
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