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The extracellular matrix in myocardial injury, repair, and remodeling
Nikolaos G. Frangogiannis
Nikolaos G. Frangogiannis
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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 3

Matricellular proteins regulate cellular responses in the pressure-overloaded myocardium.

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Matricellular proteins regulate cellular responses in the pressure-overl...
In the pressure-overloaded heart, mechanical stress activates neurohumoral pathways and induces synthesis and release of matricellular macromolecules, including TSP1, -2, and -4, tenascin-C, OPN, SPARC, and periostin. Matricellular proteins have been implicated in regulation of matrix assembly, in transduction of mechanosensitive signaling, and in the pathogenesis of fibrosis and cardiac hypertrophy, and may also modulate survival of cardiomyocytes under conditions of stress. The effects of the matricellular proteins are exerted through direct activation of cell surface receptors or through modulation of growth factor– and protease-mediated responses.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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