JACC Focus Seminar: Extracellular Matrix in Cardiovascular Health and Disease
JACC Focus Seminar
Extracellular Matrix in Ischemic Heart Disease, Part 4/4: JACC Focus Seminar

https://doi.org/10.1016/j.jacc.2020.03.020Get rights and content
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Highlights

  • Myocardial ischemia and infarction are associated with dynamic changes in the composition of the ECM network.

  • In addition to their structural role, ECM proteins modulate cellular phenotype and function.

  • Specialized matrix proteins transduce signals that regulate inflammation, fibrosis, and angiogenesis.

  • Targeting the ECM may attenuate remodeling and enhance repair and regeneration following infarction.

Abstract

Myocardial ischemia and infarction, both in the acute and chronic phases, are associated with cardiomyocyte loss and dramatic changes in the cardiac extracellular matrix (ECM). It has long been appreciated that these changes in the cardiac ECM result in altered mechanical properties of ischemic or infarcted myocardial segments. However, a growing body of evidence now clearly demonstrates that these alterations of the ECM not only affect the structural properties of the ischemic and post-infarct heart, but they also play a crucial and sometimes direct role in mediating a range of biological pathways, including the orchestration of inflammatory and reparative processes, as well as the pathogenesis of adverse remodeling. This final part of a 4-part JACC Focus Seminar reviews the evidence on the role of the ECM in relation to the ischemic and infarcted heart, as well as its contribution to cardiac dysfunction and adverse clinical outcomes.

Key Words

biomarker
collagen
fibroblast
heart failure
ischemic heart disease

Abbreviations and Acronyms

ECM
extracellular matrix
MI
myocardial infarction
MIF
myocardial interstitial fibrosis
MMP
matrix metalloprotease
PGP
proline-glycine-proline
TGF
transforming growth factor
VEGF
vascular endothelial growth factor

Cited by (0)

Dr. Frangogiannis’ laboratory is supported by National Institutes of Health grants R01HL76246 and R01HL85440 and by grants PR151029, PR151134, and PR181464 from the Department of Defense Congressionally Directed Medical Research Programs. Dr. Kovacic has received research support from the National Institutes of Health (R01HL130423, R01HL135093). Thomas Wight, MD, served as Guest Associate Editor for this paper.

Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.