The inflammatory response in myocardial injury, repair, and remodelling

Research output: Contribution to journalArticle

378 Citations (Scopus)

Abstract

Myocardial infarction triggers an intense inflammatory response that is essential for cardiac repair, but which is also implicated in the pathogenesis of postinfarction remodelling and heart failure. Signals in the infarcted myocardium activate toll-like receptor signalling, while complement activation and generation of reactive oxygen species induce cytokine and chemokine upregulation. Leukocytes recruited to the infarcted area, remove dead cells and matrix debris by phagocytosis, while preparing the area for scar formation. Timely repression of the inflammatory response is critical for effective healing, and is followed by activation of myofibroblasts that secrete matrix proteins in the infarcted area. Members of the transforming growth factor 2 family are critically involved in suppression of inflammation and activation of a profibrotic programme. Translation of these concepts to the clinic requires an understanding of the pathophysiological complexity and heterogeneity of postinfarction remodelling in patients with myocardial infarction. Individuals with an overactive and prolonged postinfarction inflammatory response might exhibit left ventricular dilatation and systolic dysfunction and might benefit from targeted anti-IL-1 or anti-chemokine therapies, whereas patients with an exaggerated fibrogenic reaction can develop heart failure with preserved ejection fraction and might require inhibition of the Smad3 (mothers against decapentaplegic homolog 3) cascade. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to rationally implement inflammation-modulating strategies.

Original languageEnglish (US)
Pages (from-to)255-265
Number of pages11
JournalNature Reviews Cardiology
Volume11
Issue number5
DOIs
StatePublished - 2014

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Chemokines
Wounds and Injuries
Heart Failure
Myocardial Infarction
Smad Proteins
Inflammation
Myofibroblasts
Complement Activation
Toll-Like Receptors
Transforming Growth Factors
Interleukin-1
Phagocytosis
Cicatrix
Dilatation
Reactive Oxygen Species
Myocardium
Leukocytes
Up-Regulation
Biomarkers
Cytokines

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The inflammatory response in myocardial injury, repair, and remodelling. / Frangogiannis, Nikolaos G.

In: Nature Reviews Cardiology, Vol. 11, No. 5, 2014, p. 255-265.

Research output: Contribution to journalArticle

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