Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 127, Issue 5, Pages 1600-1612Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI87491
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Funding
- NIH [R01 HL76246, R01 HL85440]
- Department of Defense Congressionally Directed Medical Research Programs (CDMRP) [PR151134, PR151029]
- CDMRP [PR151029, 893773, PR151134, 893782] Funding Source: Federal RePORTER
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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.
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