Table 1.

Studies of Chymase Inhibition in Mice, Rats, Hamsters and Humans

Condition	Model	Chymase inhibition effects	Reference
Intermittent Hypoxia	mouse	Decreased perivascular fibrosis and cardiomyocyte hypertrophy, inflammatory cytokines, oxidative stress, Ang II, and superoxide production in LV myocardium	[127]
Dextran sodium sulfate-induced colitis	mouse	Decreased neutrophil infiltration and MMP-9 activity resulting in improved disease activity index and histological scores	[128]
Ang II induced aneurysm	ApoE-deficient mouse	Decreased MMP-9 activity and macrophage infiltration. Prevented Ang II-induced aortic aneurysm formation in ApoE-deficient mice	[129]
Increased salt diet	mouse	Suppressed hypertension and decreased plasma Ang II and aldosterone	[110]
Myosin-immunized myocarditis	rat	Decreased MMP-9 activation, TGF-β expression, and macrophage infiltration; Improved survival and LV function 4 weeks after immunization	[130]
Stroke-Prone SHR	rat	Decreased aortic MMP-9 activity, TNF-α, MCP-1 levels and macrophage infiltration; Improved vascular function in vitro and survival	[113]
Indomethacin-induced colitis	rat	Decreased intestinal wall MMP-9 activation and myeloperoxidase activity; Decreased intestinal lesions and damage	[131]
Lipopolysaccharide induced liver injury	hamster	Improved liver function and reduced liver necrosis and fibrosis; Decreased liver MMP-9 activation and myeloperoxidase and TNF-α levels	[132]
Carbon tetrachloride-induced chronic liver failure	hamster	Decreased liver myofibroblasts and fibrosis and decreased liver Ang II levels	[133]
Elastase-induced aneurysm formation	hamster	Decreased abdominal aortic aneurysm size and mast cell infiltration	[134]
Streptozotocin-induced diabetes	hamster	Decreased LV NOX4-induced oxidative stress, malonaldehyde levels, and interstitial fibrosis; Attenuated kidney oxidative stress, decreased renal fibrosis and TGF-β, and improved renal function	[135-137]
Cigarette smoking and bleomycin-induced lung injury	hamster	Decreased lung TGF-β signaling, ET-1 levels, and pulmonary hypertension and fibrosis	[138, 139]
Coronary artery ligation	hamster	Improved LV systolic function and hemodynamics, hypertrophy and fibrosis; Improved survival	[90,91,140]
Obstructed kidney	hamster	Attenuated tubulointerstitial fibrosis and TGF-β and α-smooth muscle actin expression	[141]
Prolonged high-fat diet	hamster	Prevented lipid deposition in the aortas	[142]
Cardiac Ischemia Reperfusion	mouse	Decrease infarction size and improved LV function	[94]
Cardiac Ischemia Reperfusion	pig	Decreased myocardial infarction size and tissue MMP-9 activity	[89]
Cardiac Ischemia Reperfusion	dog	Decreased troponin, MMP-9 activity, and cardiac interstitial chymase activity and attenuated mitochondrial damage	[88]
Post-Transmural Myocardial Infarction	human	Did not improve LVEF or LV volumes six months after drug initiation 5-10 days after myocardial infarction	[86,87]
Hypertension	human	Polygonum inhibition of chymase caused a depressor effect especially in hypertensive subjects with excessive salt intake	[143]
Carotid artery bypass	dog	Inhibited vascular proliferation in grafted vein	[144]
Orally active chymase inhibitor	hamster	Suppressed heart chymase activity	[145]

Abbreviations: LV - Left ventricular, LVEF - Left ventricular ejection fraction, TNF – Tumor necrosis factor, MMP-9 Matrix metallopeptidase 9, MCP-1 - Mast cell protease 1, NOX4 - NADPH oxidase 4, ET-1 – Endothelin 1.