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

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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.