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Repair of the Infarcted Myocardium

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Introduction to Translational Cardiovascular Research

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Abstract

The adult mammalian heart has negligible regenerative capacity; thus, sudden death of a large number of cardiomyocytes in the infarcted myocardium leads to replacement of dead cells with collagen-based scar. Repair of the infarcted heart can be divided into three distinct, but overlapping phases: the inflammatory phase, the proliferative phase and the maturation phase. Cardiomyocyte necrosis and matrix fragmentation in the infarcted myocardium release damage-associated molecular patterns (DAMPs) that activate innate immune cascades and trigger the inflammatory reaction. Induction of chemokines and cytokines is a hallmark of the post-infarction inflammatory response mediating recruitment of neutrophils and mononuclear cells in the myocardium. As infiltrating leukocytes clear the wound from dead cells and matrix debris, pro-inflammatory signaling is repressed and fibroblasts undergo myofibroblast conversion. Induction of specialized matricellular proteins that modulate growth factor and cytokine responses plays a critical role in activation of reparative cells and in formation of the scar. Cross-linking of the collagen-based matrix marks the end of the proliferative phase, as the scar matures and most fibroblasts and vascular cells in the wound undergo apoptosis. This chapter provides an overview of the phases of repair in the infarcted heart. Moreover, we discuss challenges and opportunities in targeting the inflammatory and reparative response following infarction in order to attenuate adverse remodeling and to prevent progression of post-infarction heart failure.

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Abbreviations

AMI:

Acute myocardial infarction

DAMPs:

Damage-associated molecular patterns

GM-CSF:

Granulocyte Macrophage-Colony Stimulating Factor

HF:

Heart failure

HIF-1α:

Hypoxia-Inducible Factor

HSPs:

Heat shock proteins

ICAM-1:

Intercellular Adhesion Molecule 1

IL:

Interleukin

INFL:

Inflammation

IRAK-M:

Interleukin-1 receptor associated kinase

MCP:

Monocyte Chemoattractant Protein

M-CSF:

Macrophage-Colony Stimulating Factor

MI:

Myocardial infarction

MMP:

Matrix metalloproteinase

PAI-1:

Plasminogen Activator Inhibitor

REM:

Cardiac remodeling

ROS:

Reactivate Oxygen Species

SCF:

Stem Cell Factor

SDF:

Stromal Derived Factor

SOD:

Superoxide dismutase

TGF-β:

Transforming growth factor-β

TIMP-1:

Tissue Inhibitor of Metalloproteinases

TLRs:

Toll-like receptors

TNF-α:

Tumor Necrosis Factor-α

TSP-1:

Thrombospondin-1

VEGF:

Vascular Endothelial Growth Factor

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Acknowledgments

Dr Frangogiannis’ laboratory is funded by NIH grants R01 HL76246 and R01 HL85440 and by the Wilf Family Cardiovascular Research Institute.

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  1. Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, 1300 Morris Park Avenue Forchheimer G46B, Bronx, NY, 10461, USA

    Junhong Wang & Nikolaos G. Frangogiannis MD

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  1. Junhong Wang
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  2. Nikolaos G. Frangogiannis MD
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Correspondence to Nikolaos G. Frangogiannis MD .

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  1. Academy of Athens, Biomedical Research Foundation, Athens, Greece

    Dennis V. Cokkinos

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© 2015 Springer International Publishing Switzerland

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Wang, J., Frangogiannis, N.G. (2015). Repair of the Infarcted Myocardium. In: Cokkinos, D. (eds) Introduction to Translational Cardiovascular Research. Springer, Cham. https://doi.org/10.1007/978-3-319-08798-6_16

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  • DOI: https://doi.org/10.1007/978-3-319-08798-6_16

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