Targeting the inflammatory response in healing myocardial infarcts

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Healing of myocardial infarcts depends on an inflammatory cascade that ultimately results in clearance of dead cells and matrix debris and formation of a scar. Myocardial necrosis activates complement, Nuclear Factor (NF)-κB and Toll-like Receptor (TLR)-dependent pathways, and generates free radicals, triggering an inflammatory response. Chemokines and cytokines are markedly induced in the infarct and mediate recruitment and activation of neutrophils and mononuclear cells. Extravasation of platelets and plasma proteins, such as fibrinogen and fibronectin, results in formation of a clot, consisting of platelets embedded in a mesh of crosslinked fibrin. This provisional matrix provides a scaffold for migration of cells into the infarct. Monocytes differentiate into macrophages and secrete fibrogenic and angiogenic growth factors inducing formation of granulation tissue, containing myofibroblasts and neovessels. Repression of proinflammatory cytokine and chemokine synthesis, mediated in part through Transforming Growth Factor (TGF)-β and Interleukin (IL)-10, is critical for resolution of the inflammatory infiltrate and transition to fibrous tissue deposition. Infarct myofibroblasts deposit extracellular matrix proteins and a collagen-based scar is formed. As the wound matures, fibroblasts undergo apoptosis and neovessels regress, resulting in formation of a scar with a low cellular content containing dense, cross-linked collagen. The pathologic and structural changes associated with infarct healing directly influence ventricular remodeling and affect prognosis in patients with myocardial infarction. Understanding the mechanisms involved in the regulation of the post-infarction inflammatory response, and the spatial and temporal parameters of wound healing is necessary in order to identify specific molecular targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)1877-1893
Number of pages17
JournalCurrent Medicinal Chemistry
Volume13
Issue number16
DOIs
StatePublished - Jul 2006
Externally publishedYes

Fingerprint

Platelets
Chemokines
Cicatrix
Collagen
Myofibroblasts
Myocardial Infarction
Tissue
Cytokines
Granulation
Macrophages
Extracellular Matrix Proteins
Toll-Like Receptors
Transforming Growth Factors
Fibroblasts
Blood Platelets
Fibrin
Fibronectins
Debris
Scaffolds
Interleukin-10

Keywords

  • Chemokine
  • Cytokine
  • Extracellular matrix
  • Infarction
  • Inflammation
  • Macrophage
  • Neutrophil
  • Remodeling

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Targeting the inflammatory response in healing myocardial infarcts. / Frangogiannis, Nikolaos G.

In: Current Medicinal Chemistry, Vol. 13, No. 16, 07.2006, p. 1877-1893.

Research output: Contribution to journalArticle

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