Chymase plays a crucial role in
angiotensin II formation in various tissues.
Angiotensin II induces gene expressions of
transforming growth factor (TGF)-β and
matrix metalloproteinase (MMP)-9, and
chymase also converts precursors of TGF-β and MMP-9 to their active forms. All of
angiotensin II, TGF-β and MMP-9 are considered to be closely involved in the development and progression of
metabolic syndrome and its complications. In a diabetic animal model,
chymase induced pancreatic disorganization via attack of oxidative stress induced by augmentation of
chymase-forming
angiotensin II. In atherosclerotic lesions in patients, accumulation of
chymase-positive cells was observed, and
chymase inhibition prevented the development of
atherosclerosis in an animal model. In
Apo E-deficient mice,
chymase inhibition prevents the development of
angiotensin II-induced abdominal aneurysmal aorta (AAA). In this model, the AAA development on an increase in MMP-9 activities induced by
angiotensin II, but the inhibition of MMP-9 activation by
chymase inhibitor resulted in attenuation of the AAA development. Cardiac dysfunction after
myocardial infarction was also attenuated by
chymase inhibition. Steatosis and fiblosis in liver were strongly prevented by
chymase inhibition in an animal model with
nonalcoholic steatohepatitis which is involved in
metabolic syndrome. Therefore,
chymase inhibition may be useful for attenuating MMP-9 and TGF-β levels, in addition to reducing
angiotensin II formation, and this function may provide powerful preventions of organ damages. In this review, we propose the significance of
chymase as a target to prevent complications of
metabolic syndrome.