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The inflammatory response in myocardial injury, repair, and remodelling

Nature Reviews Cardiology volume 11, pages 255–265 (2014)Cite this article

Subjects

Key Points

  • In the infarcted myocardium, cardiomyocyte death and degradation of the cardiac extracellular matrix releases signals that activate innate immune pathways and trigger an intense inflammatory reaction

  • The role of postinfarction inflammation in extending ischaemic cardiomyocyte injury is controversial; however, inflammatory mediators are implicated in dilative remodelling and in the pathogenesis of postinfarction heart failure

  • Early stimulation of inflammatory signalling is important for clearance of dead cells from the infarcted area and for tissue repair

  • Timely repression of proinflammatory mediators protects the heart from excessive inflammatory injury

  • Patients who survive a large myocardial infarction exhibit pathophysiological heterogeneity, as subpopulations with progressive dilative remodelling or predominant diastolic dysfunction are identified

  • Biomarker-based approaches are needed to identify patients with overactive proinflammatory signalling or excessive fibrosis who might benefit from targeted therapies

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 β 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.

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Figure 1: Cytotoxic inflammatory injury after myocardial infarction.
Figure 2: The postinfarction inflammatory response.
Figure 3: TGF-β is a key mediator in postinfarction remodelling.
Figure 4: Biomarker-based approaches to target the inflammatory response in patients with acute myocardial infarction.

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Acknowledgements

Dr Frangogiannis' laboratory is funded by NIH grants R01 HL76246 and R01 HL85440 and by the Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, New York, USA.

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

    Nikolaos G. Frangogiannis

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Frangogiannis, N. The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 11, 255–265 (2014). https://doi.org/10.1038/nrcardio.2014.28

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