2002 Fiscal Year Final Research Report Summary
Molecular mechanism of atherosclerosis initiation by lipid oxidation products and its regulation by dietary components
| Project/Area Number |
13460059
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
食品科学・栄養科学
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
IMAIZUMI Katsumi Kyushu University, Faculty of Agriculture, Prof., 大学院・農学研究院, 教授 (90037466)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAGAO Kohji Saga Univ., Faculty of Agr., Assis. Prof., 農学部, 助手 (10336109)
SATO Masao Kyushu University, Faculty of Agriculture, Assis. Prof., 大学院・農学研究院, 助手 (90294909)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | lipid oxides / atherosclerosis / apo E deficient mice / isoprostanes / sterol oxides / GC / MS / ABCA1 / macrophages |
|---|
| Research Abstract |
Isoprostanes, oxidation products of polyunsaturated fatty acids, and oxisterois involve in an early stage of atherosclerosis. The amount of these oxidation products occurring in animal and human tissues is so low that it is required to develop a highly sensitive method to accurately determine them. Therefore, we have established a method with using GC/MS and studied the effect of these oxidation products on the development of atherosclerosis in apo E deficient mice. A role of diet in preventing from atherosclerosis was also examined as follows.
(1) There were no direct relationships between the lesion size and the isoprostane, (8-isoPGF2α and dinor) levels in apo E-deficient mice as well as the wild type strain. Dietary isoflavones resulted in no significant effect on the urinary isoprostane levels, but dietary chlorogenic acid lowered the urinary excretion of isoprostanes. These results cast doubt on a role of isoprostanes as biomarker for in vivo peroxidation. (2) We have confirmed a role of 22-hydroxycholesterol as a ligand for transcription factor LXR, since the oxide resulted in an increased export of cholesterol from the culture macrophages and an increased expression of ABCA1 which contains the responsive element for LXR. We also found oxidation products from cholesterol and plant sterols that led to an increase of exporting cholesterol from the macrophages. (3) Among the dietary components tested, isoflavones resulted in a decrease in the expression of macrophage chemoattractant protein in the aorta.
|
