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ROLE OF FEMALE HORMONE AND FOOD FACTORS IN PREVENTION OF ATHEROSCLEROSIS -INVESTIGATIONS USING KNOCKOUT MICE

Research Project

Project/Area Number 12680149
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 食生活
Research InstitutionNAKAMURA GAKUEN UNIVERSITY

Principal Investigator

HARA Takayuki  NAKAMURA GAKUEN UNIVERSITY ASSOCIATE PROFESSOR, 栄養科学部, 助教授 (10164998)

Co-Investigator(Kenkyū-buntansha) TAKESHIMA Mikako  NAKAMURA GAKUEN UNIVERSITY RESEARCH ASSISTANT, 栄養科学部, 助手 (00241183)
HARADA Nobuhiro  FUJITA HEALTH UNIVERSITY PROFESSOR, 医学部, 教授 (00189705)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsFEMALE HORMONE / ESTROGEN / ATHEROSCLEROSIS / KNOCKOUT MOUSE / AROMATASE / FOOD FACTORS / PREVENTION / CHOLESTEROL / アロマターゼ
Research Abstract

It is well known that the incidence of cardiovascular diseases such as ischemic heart disease and atherosclerosis is higher in the post-menopausal women than in the menopausal women. The reason is explained by the fact that the serum level of female hormone, estrogen is decreased very much in the post-menopausal women, and the decrease must be related to the pathogenesis of atherosclerosis. Estrogen is produced from testosterone by the enzymatic catalysis of aromatase cytochrome P-450 which exists in the ovary. We found from our investigation in 2000〜2001 that atherosclerosis cannot be observed in aromatase knockout mice fed on a high cholesterol and high fat diet for 4 months. Mouse is an animal of rat type whose major plasma lipoprotein is HDL, atheroprotective lipoprotein, thereby the incidence of atherosclerosis is very rare in mice. These findings suggest that the deficiency of estrogen itself may not be a sole factor of the pathogenesis of atherosclerosis in mice. We are now trying to make a new model mouse, a double knockout mouse whose genes of both apo E and aromatase are destroyed. It is known that soy protein isolate (SPI) which contains isoflavone is anti-atherogenic. We prepared isoflavone-free SPI (IF-SPI) using ion exchange column chromatography after extraction of SPI with water. We kept apo E-knockout mice (8 months old) fed on a diet with SPI or IF-SPI for 3 weeks. The plasma total cholesterol in apo E-knockout mice fed on an SPI-diet was decreased compared with the mice on an IF-SPI diet. On the contrary, HDL-cholesterol was increased with an SPI-diet. The extent of atherosclerosis in the case of SPI-diet was weaker than in the case of IF-SPI diet. These results suggest that isoflavone itself rather than soy protein has atheroprotective effect.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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