| Project/Area Number |
09306024
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | FOUNDATION FOR ADVANCEMENT OF INTERNATIONAL SCIENCE (1999)
University of Tsukuba (1997-1998) |
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Principal Investigator |
MURAKAMI Kazuo Foundation for Advancement of International Science Executive Director, 専任研究員 (70110517)
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| Co-Investigator(Kenkyū-buntansha) |
HORIGUCHI Hisasi Medical Univ. Ibaraki Pref., Instructor, 保健医療学部, 助手 (30238795)
KASUYA Yoshitoshi Basic Medicine, Univ. of Tsukuba, Assist. Prof., 基礎医学系, 講師 (70221877)
FUKAMIZU Akiyoshi Inst. Of Applied Biochem., Univ. of Tsukuba, Prof., 応用生物化学系, 教授 (60199172)
杉山 文博 筑波大学, 基礎医学系, 講師 (90226481)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | Tsukuba hypertensive mouse / malignant hypertension / Vascular remodeling / renin-angiotensin system / transgenic mouse / 腎臓 / 大動脈瘤 / 動脈硬化症 / コレステロール / 脂肪 / アンギオテンシンII / 受容体 / レニン / 高血圧 / アンジオテンシノーゲン / 妊娠 / トランスジェニックマウス / アンジオテンシンII / 臓器傷害 |
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| Research Abstract |
(1) The Tsukuba hypertensive mouse as a model of human malignant hypertension
The renin-angiotensin, system has a pivotal role in hypertension. The Tsukuba hypertensive mouse (THM; a transgenic mouse carrying human genes for both renin and angiotensinogen) was generated to allow further examination of the renin-angiotensin system in a variety of pathologic conditions. We evaluated the development of renal lesions in these mice and in controls by morphometric, immunohistochemical and ultra-structural methods. Blood pressure was significantly higher in THM than in control mice; 1 year after birth, it was approximately 40 mmHg higher. The kidney-to-body weight ratio was also higher in THM than in control. Morphometrical analysis revealed that the glomerular sclerosis index was significantly elevated in THM with 10% of the glomeruli sclerotic at 18 months. The grade of vascular lesion and the frequency of fibronoid arteritis of the kidney exhibited the same tendency as the glomerular sclerosis index. Light and electron microscopy revealed significant fibrinoid arteritis of the kidney in THM and also "onion skinning" , both pathognomonic for malignant nephrosclerosis. THM may be an excellent model of human malignant hypertension.
(2) Vascular remodeling in hypertensive transgenic mice
We physiologically and histopathologically analyzed vascular damage due to hyper' tension and vascular remodeling in hypertensive transgenic mice (THM). Pubertal(8-week -old) THM already had hypertension similar to blood pressure in adult THM due to an enhanced renin angiotensin system (RAS). They progressively developed remarkable vascular hypertrophy composed of dedifferentiation of vascular smooth muscle cells (VSMCs) and extracellular matrix accumulation in the thoracic aorta, and VSHC hyperplasia was predominant in the abdominal aorta. THM are therefore a useful animal model for studying vascular remodeling mediated by enhanced RAS.
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