Impact of mast cell chymase on renal disease progression

Haimanot Wasse*, Nawazish Naqvi, Ahsan Husain

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Chymase, a serine protease found in mast cell granules, is released into the interstitium following injury or inflammation. Chymase is the primary ACE-independent pathway of angiotensin II formation, and also functions to activate TGF-beta and other promoters of extracellular matrix degradation, thereby playing a role in tissue remodeling. In the diseased kidney, chymase-containing mast cells markedly increase and their density correlates with tubulointerstitial fibrosis severity. Studies in humans support the pathologic role of chymase in diabetic nephropathy, while animal studies form the basis for the importance of increased chymase-dependent angiotensin II formation in progressive hypertensive, diabetic and inflammatory nephropathies. Moreover, humans with kidney disease express chymase in diseased blood vessels in concordance with significantly elevated plasma chymase levels. Conversely, specific chymase inhibitors attenuate angiotensin II production and renal fibrosis in animal models, suggesting their potential therapeutic benefit in human nephropathy, where chymase-containing mast cells accumulate and contribute to progressive disease.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalCurrent Hypertension Reviews
Volume8
Issue number1
DOIs
StatePublished - 2012

Keywords

  • Angiotensin II
  • Chymase
  • Kidney disease
  • Mast cells
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Internal Medicine

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