Targets of chymase inhibitors

Expert Opin Ther Targets. 2011 Apr;15(4):519-27. doi: 10.1517/14728222.2011.555401. Epub 2011 Feb 4.

Abstract

Introduction: Chymase converts angiotensin I to angiotensin II and it can also convert precursors of TGF-β and MMP-9 to their active forms. Therefore, diseases related to angiotensin II TGF-β, and MMP-9 could potentially be treated with chymase inhibitors.

Areas covered: This review discusses the appropriate targets and safety of chymase inhibitors. Six diseases with notable mortality or morbidity as targets of chymase inhibitors are focused on; abdominal aortic aneurysms (AAAs), nephropathy and retinopathy, cardiomyopathy, nonalcoholic steatohepatitis (NASH), organ fibrosis and intestinal diseases.

Expert opinion: If chymase inhibition proves to be a useful strategy for the attenuation of angiotensin II, TGF-β and MMP-9 in vivo, the application of chymase inhibitors is likely to become widespread in various diseases in the clinical setting. Chymase inhibitors are anticipated not to interfere with the homeostasis of resting tissues, that is, those not affected by injury or inflammation.

Publication types

  • Review

MeSH terms

  • Angiotensin II / metabolism
  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism
  • Chymases / antagonists & inhibitors*
  • Chymases / metabolism
  • Digestive System Diseases / drug therapy
  • Digestive System Diseases / metabolism
  • Enzyme Inhibitors / therapeutic use*
  • Fibrosis / drug therapy
  • Fibrosis / metabolism
  • Humans
  • Intestinal Diseases / drug therapy
  • Intestinal Diseases / metabolism
  • Matrix Metalloproteinase 9 / metabolism*
  • Molecular Targeted Therapy
  • Transforming Growth Factor beta / metabolism*

Substances

  • Enzyme Inhibitors
  • Transforming Growth Factor beta
  • Angiotensin II
  • Chymases
  • Matrix Metalloproteinase 9