| Co-Investigator(Kenkyū-buntansha) |
HARADA Nobuhiro FIJITAHEALTH UNIVERSITY, MEDICINE, PROFESSOR, 医学部医学科, 教授 (00189705)
TAKESHIMA Mikako NAKAMURA GAKUEN UNIVERSITY, NUTRITION, RESEARCH ASSISTANT, 栄養科学部栄養科学科, 助手 (00241183)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
In mice whose gene for female hormone synthase, aromatase (AR) was knocked out (ARKO mice), estrogen cannot be detected in the serum. The abnormal development of ovary is observed in the female mice, and the fat liver is observed in both sex mice. Thus, the mice are expected to be a good animal model for the study of atherosclerosis which depends on estrogen deficiency. It has been shown that atherosclerotic lesions were not observed in ARKO mice which were kept on the high cholesterol diet, as well as normal mice. Since mouse is a rat type animal, in which HDL content is very high in the serum, atherosclerotic lesions are not observed in the mouse not like an atherogenic animal, human or rabbit in which HDL content is very low in the serum. Therefore, atherosclerotic lesions may be hardly observed in ARKO mice deficient in female hormone, estrogen.
It has been shown that mice deficient in apo E gene which produces a component of apolipoproteins of HDL is a good model animal for the stu
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dy of atherosclerosis characterized by atheroma, because the atherosclerosis was spontaneously observed in the mice even with a normal diet. In this study, we tried to make a new animal model using AR and Apo E deficient mice (DBKO mice) to see whether or not estrogen deficiency acts as a positive factor of pathogenesis of atherosclerosis. Total cholesterol contents in the serum of DBKO mice were as follows : ♂, 1368±638mg/dl (n=8) ; ♀, 704±245mg/dl (n=7). The triglyceride contents in the serum were as follows : ♂, 969±869mg/dl (n=8) : ♀, 251±121mg/dl (n=7). These results indicate that DBKO mice are clearly more hyperlipidemic than apo E decicient mice. We tried to observe the lesions of artery of DBKO mice. In Apo E KO mice, atherosclerotic lesions expressed as % of area were 38±7% (n=9), 39±7% (n=11) in male and female mice, respectively, whereas those in DBKO mice were 28±6% (n=12), 16±8% (n=8) in male and female mice, respectively. These observations suggest that aromatase gene deficiency of apo E KO mice results on the decrease of atherosclerosis of the arterial wall. The reasons are not understood well at this point, but in this animal model, cholesterol itself may not be a sole factor of atherosclerosis. The discrepancy should be clarified in the near future. Less
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