RAS inhibition in resident fibroblast biology

Alexandra M. Garvin, Bilal S. Khokhar, Michael P. Czubryt, Taben M. Hale

Research output: Contribution to journalArticlepeer-review

Abstract

Angiotensin II (Ang II) is a primary mediator of profibrotic signaling in the heart and more specifically, the cardiac fibroblast. Ang II-mediated cardiomyocyte hypertrophy in combination with cardiac fibroblast proliferation, activation, and extracellular matrix production compromise cardiac function and increase mortality in humans. Profibrotic actions of Ang II are mediated by increasing production of fibrogenic mediators (e.g. transforming growth factor beta, scleraxis, osteopontin, and periostin), recruitment of immune cells, and via increased reactive oxygen species generation. Drugs that inhibit Ang II production or action, collectively referred to as renin angiotensin system (RAS) inhibitors, are first line therapeutics for heart failure. Moreover, transient RAS inhibition has been found to persistently alter hypertensive cardiac fibroblast responses to injury providing a useful tool to identify novel therapeutic targets. This review summarizes the profibrotic actions of Ang II and the known impact of RAS inhibition on cardiac fibroblast phenotype and cardiac remodeling.

Original languageEnglish (US)
Article number109903
JournalCellular Signalling
Volume80
DOIs
StatePublished - Apr 2021

Keywords

  • Angiotensin converting enzyme inhibitor
  • Angiotensin II
  • Angiotensin receptor antagonist
  • Fibroblast
  • Fibrosis

ASJC Scopus subject areas

  • Cell Biology

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