Human Chymase Expression in a Mice Induces Mild Hypertension with Left Ventricular Hypertrophy

Koga, Takafumi; Urata, Hidenori; Inoue, Yukiko; Hoshino, Takafumi; Okamoto, Takehiro; Matsunaga, Akira; Suzuki, Misao; Miyazaki, Jun‐ichi; Ideishi, Munehito; Arakawa, Kikuo; Saku, Keijiro

doi:10.1291/hypres.26.759

Cited by 18 publications

(21 citation statements)

References 41 publications

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“…A transgenic mouse model carrying the human chymase gene was observed to have elevated blood pressure, and its hypertension was abolished by an ARB (10). Koga et al (30) demonstrated that in vivo expression of human chymase in mice caused mild hypertension with left ventricular hypertrophy and also chronic inflammatory changes. Moreover, they reported that chymase-dependent angiotensin II formation was also observed in the wild-type littermates.…”

Section: Fig 4 Angiotensin I-induced Vasoconstrictions In Isolated mentioning

confidence: 99%

Role of Chymase-Dependent Angiotensin II Formation in Regulating Blood Pressure in Spontaneously Hypertensive Rats

et al. 2005

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Vascular smooth muscle cells in spontaneously hypertensive rats (SHR) express angiotensin II-forming chymase (rat vascular chymase [RVCH]), which may contribute to blood pressure regulation. In this study, we studied whether chymase-dependent angiotensin II formation contributes to the regulation of blood pressure in SHR. The systolic blood pressure in 16-week-old Wistar-Kyoto (WKY) rats was 113 ± 9 mmHg, compared to 172 ± 3 mmHg in SHR. Using synthetic substrates for measuring angiotensin-converting enzyme (ACE) and chymase activities, it was found that both ACE and chymase activities in extracts from SHR aortas were significantly higher than in those from WKY rat aortas. Using angiotensin I as a substrate, angiotensin II formation in SHR was found to be significantly higher than that in WKY rats, and its formation was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. RVCH mRNA expression could not be detected in aorta extracts from either WKY rats or SHR. In carotid arteries isolated from WKY rats and SHR, angiotensin I-induced vasoconstriction was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. Angiotensin I-induced pressor responses in both WKY rats and SHR were also completely inhibited by an ACE inhibitor, but they were not affected by a chymase inhibitor. In SHR, an ACE inhibitor and an angiotensin II receptor blocker showed equipotent hypotensive effects, but a chymase inhibitor did not have a hypotensive effect. These results indicated that chymase-dependent angiotensin II did not regulate blood pressure in SHR in the present study. (Hypertens Res 2005; 28: 457-464)

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Section: Fig 4 Angiotensin I-induced Vasoconstrictions In Isolated mentioning

confidence: 99%

Role of Chymase-Dependent Angiotensin II Formation in Regulating Blood Pressure in Spontaneously Hypertensive Rats

et al. 2005

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“…The experiment was performed in male transgenic mice (18-20 weeks of age) carrying the human chymase gene (Tg) 9 and male wild-type C57BL/6 mice (WT). Preparation of the human chymase transgene and production of Tg mice were described previously in detail 9. Mice were maintained in a pathogen-free facility under controlled temperature (24±2°C) and humidity (55±5%), with a 12 hrs light/dark cycle.…”

Section: Methodsmentioning

confidence: 99%

“…We sought to investigate the possible contribution of human chymase to LPS-induced mortality. Therefore, survival rate and chymase activity in the heart and skin were measured in transgenic mice carrying the human chymase gene 9.…”

Section: Introductionmentioning

confidence: 99%

Chymase Activities and Survival in Endotoxin-Induced Human Chymase Transgenic Mice

Rafiq¹,

Fan²,

Sherajee³

et al. 2014

Int. J. Med. Sci.

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We examined the effects of overexpressed human chymase on survival and activity in lipopolysaccharide (LPS)-treated mice. Human chymase transgenic (Tg) and wild-type C57BL/6 (WT) mice were treated with LPS (0.03, 0.1 and 0.3 mg/day; intraperitoneal) for 2 weeks. Treatment with 0.03 mg LPS did not affect survival in either WT or Tg mice. WT mice were not affected by 0.1 mg/day of LPS, whereas 25% of Tg mice died. Survival of mice treated with 0.3 mg/day of LPS was 87.5% and 0% in WT and Tg, respectively. LPS-induced increases in chymase activity in the heart and skin were significantly greater in Tg than WT mice. These data suggest a possible contribution of human chymase activation to LPS-induced mortality.

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“…Overexpression of rat vascular chymase to SMC in normotensive rats and a transgenic mouse model carrying human chymase gene cause hypertension [44,45]. After myocardial infarction in dog, blood pressure were significantly suppressed by a chymase inhibitor [46].…”

Section: Role Of Chymase In Hypertensionmentioning

confidence: 99%

The Role of Chymase in Vascular Remodeling and Tissue Fibrosis

Jin¹,

Muramatsu²,

Miyazaki

2005

CHYR

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Chymase generates angiotensin II which plays a crucial role in vascular remodeling. In clinical studies, an angiotensin II receptor blocker was successful in preventing restenosis after percutaneous coronary intervention, but an angiotensin II-converting enzyme inhibitor was not. In dog, chymase activity was significantly increased in vessels injured by a balloon catheter, and a chymase inhibitor and an angiotensin II receptor blocker were effective in preventing the vascular proliferation, but an angiotensin-converting enzyme inhibitor was ineffective. Chymase also activates matrix metalloproteinase-9, and their function may play an important role in development of atherosclerosis and aneurysmal aorta. In human atherosclerosis and aneurysmal aorta, chymase activity was significantly increased. In the experimental models, chymase activity and mRNA level were also significantly increased in atherosclerotic lesions and aneurysmal aorta, but chymase inhibitors prevented the vascular remodeling. On the other hand, chymase activates latent transforming growth factor-β-binding protein to transforming growth factor-β, and its function may be related in promoting tissue fibrosis. Chymase promotes activations of angiotensin II, matrix metalloproteinase-9 and transforming growth factor-β, and chymase inhibitors may promise to prevent vascular remodeling and tissue fibrosis.

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Human Chymase Expression in a Mice Induces Mild Hypertension with Left Ventricular Hypertrophy

Cited by 18 publications

References 41 publications

Role of Chymase-Dependent Angiotensin II Formation in Regulating Blood Pressure in Spontaneously Hypertensive Rats

Role of Chymase-Dependent Angiotensin II Formation in Regulating Blood Pressure in Spontaneously Hypertensive Rats

Chymase Activities and Survival in Endotoxin-Induced Human Chymase Transgenic Mice

The Role of Chymase in Vascular Remodeling and Tissue Fibrosis

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