Integrins in cardiac fibrosis

Research output: Contribution to journalReview articlepeer-review

Abstract

Cells sense mechanical stress and changes in their matrix environment through the integrins, a family of heterodimeric surface receptors that bind to extracellular matrix ligands and trigger cytoskeletal remodeling, while transducing a wide range of intracellular signals. Integrins have been extensively implicated in regulation of inflammation, repair and fibrosis in many different tissues. This review manuscript discusses the role of integrin-mediated cascades in myocardial fibrosis. In vitro studies have demonstrated that β1 and αv integrins play an important role in fibrogenic conversion of cardiac fibroblast, acting through direct stimulation of FAK/Src cascades, or via accentuation of growth factor signaling. Fibrogenic actions of αv integrins may be mediated, at least in part, through pericellular activation of latent TGF-β stores. In vivo evidence supporting the role of integrin heterodimers in fibrotic cardiac remodeling is limited to associative evidence, and to experiments using pharmacologic inhibitors, or global loss-of-function approaches. Studies documenting in vivo actions of integrins on fibroblasts using cell-specific strategies are lacking. Integrin effects on leukocytes may also contribute to the pathogenesis of fibrotic myocardial responses by mediating recruitment and activation of fibrogenic macrophages. The profile and role of integrins in cardiac fibrosis may be dependent on the underlying pathologic condition. Considering their cell surface localization and the availability of small molecule inhibitors, integrins may be attractive therapeutic targets for patients with heart failure associated with prominent fibrotic remodeling.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Volume172
DOIs
StatePublished - Nov 2022

Keywords

  • Extracellular matrix
  • Fibroblast
  • Fibrosis
  • Heart failure
  • Integrin
  • Leukocyte
  • Myocardial infarction

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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