The inflammatory response in myocardial infarction

Nikolaos G. Frangogiannis, C. Wayne Smith, Mark L. Entman

Research output: Contribution to journalArticle

1536 Citations (Scopus)

Abstract

One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the inflammatory response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-α release. If reperfusion of the infarcted area is initiated, it is attended by an intense inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the inflammatory response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute inflammatory response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.

Original languageEnglish (US)
Pages (from-to)31-47
Number of pages17
JournalCardiovascular Research
Volume53
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Myocardial Infarction
Cytokines
Reperfusion
Cicatrix
Myocardium
Neutrophils
Necrosis
Leukocyte Rolling
Selectins
Myocardial Reperfusion
Fibroblast Growth Factors
Neutrophil Infiltration
Chemokine CCL2
Complement Activation
Wounds and Injuries
Intercellular Adhesion Molecule-1
Therapeutics
Cardiology
Interleukin-8
Cardiac Myocytes

Keywords

  • Cytokines
  • Infarction
  • Infection/inflammation
  • Ischemia
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The inflammatory response in myocardial infarction. / Frangogiannis, Nikolaos G.; Smith, C. Wayne; Entman, Mark L.

In: Cardiovascular Research, Vol. 53, No. 1, 2002, p. 31-47.

Research output: Contribution to journalArticle

Frangogiannis, Nikolaos G. ; Smith, C. Wayne ; Entman, Mark L. / The inflammatory response in myocardial infarction. In: Cardiovascular Research. 2002 ; Vol. 53, No. 1. pp. 31-47.
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