The mechanistic basis of infarct healing

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

Myocardial infarction triggers an inflammatory cascade that results in healing and replacement of the damaged tissue with scar. Cardiomyocyte necrosis triggers innate immune mechanisms eliciting Toll-like receptor-mediated responses, activating the complement cascade and generating reactive oxygen species. Subsequent activation of NF-κB is a critical element in the regulation of cytokine, chemokine, and adhesion molecule expression in the ischemic myocardium. Chemokine induction mediates leukocyte recruitment in the myocardium. Pleiotropic proinflammatory cytokines, such as TNF-α, IL-I, and IL-6, are also upregulated in the infarct and exert a wide range of effects on a variety of cell types. Timely repression of proinflammatory gene synthesis is crucial for optimal healing; IL-10 and TGF-β-mediated pathways may be important for suppression of chemokine and cytokine expression and for resolution of the leukocytic infiltrate. In addition, TGF-β may be critically involved in inducing myofibroblast differentiation and activation, promoting extracellular matrix protein deposition in the infarcted area. The composition of the extracellular matrix plays an important role in regulating cell behavior. Both structural and matricellular proteins modulate cell signaling through interactions with specific surface receptors. The molecular and cellular changes associated with infarct healing directly influence ventricular remodeling and affect rognosis in patients with myocardial infarction.

Original languageEnglish (US)
Pages (from-to)1907-1939
Number of pages33
JournalAntioxidants and Redox Signaling
Volume8
Issue number11-12
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Chemokines
Cytokines
Myocardium
Chemical activation
Myocardial Infarction
Cell signaling
Ventricular Remodeling
Myofibroblasts
Extracellular Matrix Proteins
Toll-Like Receptors
Cardiac Myocytes
Interleukin-10
Cicatrix
Extracellular Matrix
Interleukin-6
Reactive Oxygen Species
Leukocytes
Necrosis
Adhesion
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

The mechanistic basis of infarct healing. / Frangogiannis, Nikolaos G.

In: Antioxidants and Redox Signaling, Vol. 8, No. 11-12, 11.2006, p. 1907-1939.

Research output: Contribution to journalArticle

@article{c54222941bd147f5b0899ef174c7a40f,
title = "The mechanistic basis of infarct healing",
abstract = "Myocardial infarction triggers an inflammatory cascade that results in healing and replacement of the damaged tissue with scar. Cardiomyocyte necrosis triggers innate immune mechanisms eliciting Toll-like receptor-mediated responses, activating the complement cascade and generating reactive oxygen species. Subsequent activation of NF-κB is a critical element in the regulation of cytokine, chemokine, and adhesion molecule expression in the ischemic myocardium. Chemokine induction mediates leukocyte recruitment in the myocardium. Pleiotropic proinflammatory cytokines, such as TNF-α, IL-I, and IL-6, are also upregulated in the infarct and exert a wide range of effects on a variety of cell types. Timely repression of proinflammatory gene synthesis is crucial for optimal healing; IL-10 and TGF-β-mediated pathways may be important for suppression of chemokine and cytokine expression and for resolution of the leukocytic infiltrate. In addition, TGF-β may be critically involved in inducing myofibroblast differentiation and activation, promoting extracellular matrix protein deposition in the infarcted area. The composition of the extracellular matrix plays an important role in regulating cell behavior. Both structural and matricellular proteins modulate cell signaling through interactions with specific surface receptors. The molecular and cellular changes associated with infarct healing directly influence ventricular remodeling and affect rognosis in patients with myocardial infarction.",
author = "Frangogiannis, {Nikolaos G.}",
year = "2006",
month = "11",
language = "English (US)",
volume = "8",
pages = "1907--1939",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "11-12",

}

TY - JOUR

T1 - The mechanistic basis of infarct healing

AU - Frangogiannis, Nikolaos G.

PY - 2006/11

Y1 - 2006/11

N2 - Myocardial infarction triggers an inflammatory cascade that results in healing and replacement of the damaged tissue with scar. Cardiomyocyte necrosis triggers innate immune mechanisms eliciting Toll-like receptor-mediated responses, activating the complement cascade and generating reactive oxygen species. Subsequent activation of NF-κB is a critical element in the regulation of cytokine, chemokine, and adhesion molecule expression in the ischemic myocardium. Chemokine induction mediates leukocyte recruitment in the myocardium. Pleiotropic proinflammatory cytokines, such as TNF-α, IL-I, and IL-6, are also upregulated in the infarct and exert a wide range of effects on a variety of cell types. Timely repression of proinflammatory gene synthesis is crucial for optimal healing; IL-10 and TGF-β-mediated pathways may be important for suppression of chemokine and cytokine expression and for resolution of the leukocytic infiltrate. In addition, TGF-β may be critically involved in inducing myofibroblast differentiation and activation, promoting extracellular matrix protein deposition in the infarcted area. The composition of the extracellular matrix plays an important role in regulating cell behavior. Both structural and matricellular proteins modulate cell signaling through interactions with specific surface receptors. The molecular and cellular changes associated with infarct healing directly influence ventricular remodeling and affect rognosis in patients with myocardial infarction.

AB - Myocardial infarction triggers an inflammatory cascade that results in healing and replacement of the damaged tissue with scar. Cardiomyocyte necrosis triggers innate immune mechanisms eliciting Toll-like receptor-mediated responses, activating the complement cascade and generating reactive oxygen species. Subsequent activation of NF-κB is a critical element in the regulation of cytokine, chemokine, and adhesion molecule expression in the ischemic myocardium. Chemokine induction mediates leukocyte recruitment in the myocardium. Pleiotropic proinflammatory cytokines, such as TNF-α, IL-I, and IL-6, are also upregulated in the infarct and exert a wide range of effects on a variety of cell types. Timely repression of proinflammatory gene synthesis is crucial for optimal healing; IL-10 and TGF-β-mediated pathways may be important for suppression of chemokine and cytokine expression and for resolution of the leukocytic infiltrate. In addition, TGF-β may be critically involved in inducing myofibroblast differentiation and activation, promoting extracellular matrix protein deposition in the infarcted area. The composition of the extracellular matrix plays an important role in regulating cell behavior. Both structural and matricellular proteins modulate cell signaling through interactions with specific surface receptors. The molecular and cellular changes associated with infarct healing directly influence ventricular remodeling and affect rognosis in patients with myocardial infarction.

UR - http://www.scopus.com/inward/record.url?scp=33847724471&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847724471&partnerID=8YFLogxK

M3 - Article

VL - 8

SP - 1907

EP - 1939

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 11-12

ER -