Multifunctional Role of Chymase in Acute and Chronic Tissue Injury and Remodeling

Circ Res. 2018 Jan 19;122(2):319-336. doi: 10.1161/CIRCRESAHA.117.310978.


Chymase is the most efficient Ang II (angiotensin II)-forming enzyme in the human body and has been implicated in a wide variety of human diseases that also implicate its many other protease actions. Largely thought to be the product of mast cells, the identification of other cellular sources including cardiac fibroblasts and vascular endothelial cells demonstrates a more widely dispersed production and distribution system in various tissues. Furthermore, newly emerging evidence for its intracellular presence in cardiomyocytes and smooth muscle cells opens an entirely new compartment of chymase-mediated actions that were previously thought to be limited to the extracellular space. This review illustrates how these multiple chymase-mediated mechanisms of action can explain the residual risk in clinical trials of cardiovascular disease using conventional renin-angiotensin system blockade.

Keywords: angiotensin II; chymases; endothelial cells; mast cells; renin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Acute Disease
  • Angiotensin II / metabolism
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / enzymology*
  • Cardiovascular Diseases / pathology
  • Chronic Disease
  • Chymases / antagonists & inhibitors*
  • Chymases / physiology*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Mast Cells / metabolism
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • Vascular Remodeling / drug effects
  • Vascular Remodeling / physiology*


  • Angiotensin Receptor Antagonists
  • Enzyme Inhibitors
  • Angiotensin II
  • Chymases