Targeting the chemokines in cardiac repair

Michele Cavalera, Nikolaos G. Frangogiannis

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Chemokines are a family of chemotactic cytokines that play an essential role in leukocyte trafficking. Upregulation of both CC and CXC chemokines is a hallmark of the inflammatory and reparative response following myocardial infarction. Release of danger signals from dying cells and damaged extracellular matrix activates innate immune pathways that stimulate chemokine synthesis. Cytokine-and chemokine-driven adhesive interactions between endothelial cells and leukocytes mediate extravasation of immune cells into the infarct. CXC chemokines (such as interleukin-8) are bound to glycosaminoglycans on the endothelial surface and activate captured neutrophils, inducing expression of integrins. CC chemokines (such as monocyte chemoattractant protein (MCP)-1) mediate recruitment of proinflammatory and phagocytotic mononuclear cells into the infarct. CC Chemokines may also regulate late infiltration of the healing infarct with inhibitory leukocytes that suppress inflammation and restrain the post-infarction immune response. Non-hematopoietic cells are also targeted by chemokines; in healing infarcts, the CXC chemokine Interferon-y inducible Protein (IP)-10 exerts antifibrotic actions, inhibiting fibroblast migration. Another member of the CXC subfamily, Stromal cell-derived Factor (SDF)-1, may protect the infarcted heart by activating pro-survival signaling in cardiomyocytes, while exerting angiogenic actions through chemotaxis of endothelial progenitors. Several members of the chemokine family may be promising therapeutic targets to attenuate adverse remodeling in patients with myocardial infarction.

Original languageEnglish (US)
Pages (from-to)1971-1979
Number of pages9
JournalCurrent pharmaceutical design
Volume20
Issue number12
DOIs
StatePublished - 2014

Keywords

  • Cardiac remodeling
  • Chemokine
  • Cytokine
  • Fibrosis
  • Leukocyte
  • Monocyte chemoattractant protein-1
  • Myocardial infarction

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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