• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Determination of the Pathophysiological Role of Human Chymase

Research Project

Project/Area Number 09307014
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionFukuoka University

Principal Investigator

ARAKAWA Kikuo  Fukuoka Univ., Sch. of Medicine, Professor, 医学部, 教授 (90078783)

Co-Investigator(Kenkyū-buntansha) SASAGURI Manabu  Fukuoka Univ., Sch. of Med., Assist. Prof., 医学部, 講師 (00178675)
URATA Hidenori  Fukuoka Univ., Sch. of Med., Assist. Prof., 医学部, 講師 (30289524)
IDESHI Munehito  Fukuoka Univ., Sch. of Med., Assoc. Prof., 医学部, 助教授 (20131807)
NODA Keita  Fukuoka Univ., Sch. of Med., Assist. Prof., 医学部, 講師 (70289536)
岡部 眞典  福岡大学, 医学部, 講師 (70258531)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥30,400,000 (Direct Cost: ¥30,400,000)
Fiscal Year 1999: ¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1998: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1997: ¥14,800,000 (Direct Cost: ¥14,800,000)
KeywordsTissue renin-angiotensin system / Chymase / ACE / Cardiovascular disease / Arteriosclerosis / Hypertensin / Myocardial infarction / Transgenic mouse / 組織レニンアンジオテシン系 / アンジオテンシン変換酵素、 / 心不全 / トランスジェニック動物 / 組織レニンアンジオテンシン系 / キマ-ゼ
Research Abstract

1. Development of an appropriate experimental animal model for the study to elucidate pathophysiological roles of human chymase.
1-(1) Hamster model:
For the study of human chymase, Syrian hamster appeared to be an appropriate model because of its similarity of chymase to human's in terms of enzymological characteristics and organ specificity (Akasu et al. 1998). Using Syrian hamsters, we found that aortic chymase activity and its mRNA of were unregulated after the induction of renovascular hypertension or high cholesterol diet. In addition, the degree of increased chymase activity was positively correlated with the degree of aortic tissue remodeling (Nakayama et al.1998, Uehara et al. 1999, 2000). Particularly there was a significant positive correlation between aortic chymase activity and serum total or LDL cholesterol levels (Uehara et al. 2000). These results indicated that high levels of circulating cholesterol might upregulate arterial chymase expression and augment the following a … More therosclerotic process.
1-(2) Development of human chymase transgenic mouse (TGM)(Koga et al. 1999)
Three independent human chymase TGM lines were established and they showed similar and significant phenotypic changes ; emaciation, leukocytosis and oligotrichia. These results suggested that human chymase overexpression might induce chronic tissue inflammation. Further investigation is on going to determine the mechanisms of each phenotypic change.
2. Changes of human chymase activity in various human cardiovascular diseases
Ang II-forming activity of the tissue homogenate significantly increased in atherosclerotic aortic lesion (Ihara et al. 1999) and post-infarction myocardium (Ihara et al. 1998). In addition, there was a positive significant correlation between arterial (internal thoracic artery) chymase activity and serum total or LDL-cholesterol levels (Uehara et al. 2000). These results suggested that local chymase-dependent Ang II formation might be upregulated by high level of circulating cholesterol. On the other hand, mast cells located in the adventitia of the aorta or in the pericardium of the heart were the main origin of chymase in human cardiovascular organs (Hoshino et al. 1999). This may imply that chymase-dependent Ang II formation in the adventitia or in the pericardium may play a important role in the following tissue remodeling. Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Niwata et al.: "Substituted 3-(Phenylsulfony1)-1-phenyl-imidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase"J. Med. Chem.. 40. 2156-2163 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 浦田秀則: "レニン・アンジオテンシン系と心血管疾患:RASとキマーゼ系"BIOClinica.. 13. 755-759 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akasu et al.: "Differences in tissue angiotensin II-forming pathways by species and organs in vitro"Hypertension.. 32. 514-520 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishimura et al.: "Functional evidence for alternative angiotensin II-forming pathways in hamster cardiovascular system"Am J Physiol.. 275. H1307-H1312 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Voors et al.: "Dual pathway for angiotensin II formation in human internal mammary arteries"Brit J Pharmacol. 125. 1028-1032 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Pfeufer et al.: "Chymase gene locus is not associated with myocardial infarction and is not linked to heart size or blood pressure"Am J Cardiol. 82. 979-981 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Urata H and Arakawa K: "Angiotensin II-forming systems in cardiovascular diseases"Heart Failure Reviews.. 3. 119-124 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 浦田秀則: "レニン-アンジオテンシン系研究の進歩1 キマーゼとアンジオテンシン変換酵素"治療学. 33. 10-13 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Urata H and Arakawa K: "Alernative pathways for angiotensin II generation in man"J Hum Hypertens.. 13 (Suppl 3). S27 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toth et al.: "Mast cells in rapidly progressive glomerulonephritis"J Am Soc Nephl.. 10. 1498-1505 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ihara et al.: "Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta"Hypertension.. 33. 1399-1405 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uehara et al.: "Increased chymase activity in internal thoracic artery of patients with hypercholesterolemia"Hypertension.. 35. 55-60 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 浦田秀則、出石宗仁、荒川規矩男: "心不全"医薬ジャーナル社. 190-199 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 浦田秀則、荒川規矩男: "高血圧年報 Review & Topics"先端医学社. 33-38 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 藤原真紀、浦田秀則、荒川規矩男: "アンジオテンシンII受容体拮抗薬 第2判"医薬ジャーナル社. 13-25 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 浦田秀則: "Key Word 1999-2000 高血圧"先端医学社. 88-89 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Niwata et al.: "Substituted 3-(Phenylsulfonyl)-1-phenyl-imidazolidine-2, 4-dione derivatives as novel nonpeptide inhibitors of human heart chyumase."J. Med. Chem.. 40. 2156-2163 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akasu et al.: "Differences in tissue angiotensin II-forming pathways by species and organs in vitro."Hypertension. 32. 514-520 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishimuta et al.: "Functional evidence for alternative angiotensin II-forming pathways in hamster cardiovascular system."Am J Physiol. 275. H1307-H1312 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Voors et al.: "Dual pathways for angiotensin II formation in human internal mammary arteries."Brit J Pharmacol. 125. 1028-1032 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Pfeufer et al.: "Chymase gene locus is not associated with myocardial infarction and is not linked size or blood pressure."Am J Cardiol. 82. 979-981 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Urata H and Arakawa K: "Angiotensin II-forming systems in cardiovascular diseases."Heart Failure Reviews. 3. 119-124 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Urata H and Arakawa K: "Alernative pathways for angiotensin II generation in man."J Hum Hypertens. 13(Suppl 3). S27 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toth et al.: "Mast cells in rapidly progressive glomerulonephritis."J Am Soc Nephl. 10. 1498-1505 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ihara et al.: "Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta."Hypertension. 33. 1399-1405 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uehara et al.: "Increased chymase activity in internal thoracic artery of patients with hypercholesterolemia."Hypertension. 35. 55-60 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 岡本健宏、等: "アンジオテンシンII産生酵素 ー最近の進歩ー"臨床科学. 33. 306-312 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] 中山 秀、等: "ヒトキマーゼ"日本臨床. 55. 217-224 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Niwata et al.: "Substituted 3-(phenylsulfony1)-1-phenyl-imidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase"J.Med.Chem.. 40. 2156-2163 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akasu et al.: "Difference in tissue angiotensin II-forming pathways by species and organs in vitro"Hypertension. 32. 514-520 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishimura et al.: "Functional evidence for alternative angiotensin II-forming pathways in hamster cardiovascular system"Am J Physiol. 275. H1307-H1312 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Voors et al.: "Dual pathway for angiotensin II formation in human internal mammary arteries"Brie J Pharmacol. 125. 1028-1032 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Pfeufer et al.: "Chymase gene locus is not associated with myocardial intarction and is not linked to heart size or blood pressure"Am J Cardiol. 82. 979-981 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Urata H and Arakawa K: "Angiotensin II-forming systems in cardiovascular diseases"Heart Failure Reviews. 3. 119-124 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Urata H and Arakawa K: "Alermatobe pathways for angiotensin II generation in man"J.Hum Hypertens. 13(Suppl 3). S27 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toth et al.: "Mast cells in rapidly progressive glomerulonephritis"J Am Soc Nephl. 10. 1498-1505 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ihara et al.: "Increased chymase-dependent angitensin II formation in human atherosclerotic aorta"Hypertension. 33. 1399-1405 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uhara et al.: "Increased chymase activity in internal thoracic artery of patiens with hypercholesterolemia"Hypertension. 35. 55-60 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akasu et al.: "Differenoes in tissue angiotensin II-forming pathways by species and organs in vitro" Hypertension. 32. 514-520 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishimura et al.: "Functional evidence for alternative angiotensin II-forming pathways in hamster cardiovasculat svstem" Am J Physiol. 275. H1307-H1312 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Voors et al.: "Dual pathway for angiotensin II formation in human internal mammary arteries" Brit J Phamacol. 125. 1028-1032 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Pfeufer el al.: "Chymase gene locus is not associated with myocardial infarction and is not linked to heart size or blood pressure" Am J Cardiol. 82. 979-981 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toth el al.: "Mast cells in rapidly progressive glomerulonephritis" J Am Soc Nephl(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Ihara et al.: "Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta" Hypertension(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Baltatu et al.: "High levels of human chymase exprssion in the pineal and pituitary glands" Brain Res.759. 269-278 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Daemen M.J.A.P.and Urata H: "Healing human myocardial infarction associated with increased chymase immunoreactivity" Heart Vessels. 12. 113-115 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sasaguri et al.: "Purification and characterization of a Kinin-and angiotensin II-forming enzyme in the dog heart" J.Hypertens.15. 675-682 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sasaguri et al.: "Amlodipine lowers blood pressure without increasing sympathetic activity or activating the renin-angiotensin system in patients with essential hypertension." Eur.J.Clin.Pharmacol.53. 197-201 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Niwata et al.: "Substituted 3-(Phenylsulfonyl)-1-phenyl-imidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase" J.Med.Chem.40. 2156-2163 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishimura et al.: "Angiotensin I converting enzyme and chymase in cardiovascular tissues" Kid.Internat.49(Suppl.55). S18-S23 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 浦田秀則: "心不全におけるアンジオテンシンII産生系 心不全" 篠山重威編 医薬ジャーナル社, 190-199 (1997)

    • Related Report
      1997 Annual Research Report

URL: 

Published: 1997-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi