1997 Fiscal Year Final Research Report Summary
Study on the antiatherogenic factor in vivo : Inhibitory mechanism of ACAT by heparinoid
| Project/Area Number |
08671168
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
YOSHINARI Mototaka Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (00191627)
|
|---|
| Project Period (FY) |
1996 – 1997
|
| Keywords | ACAT / macrophaqe / atherosclerosis / heparin / prostacyclin / diabetes mellitus |
|---|
| Research Abstract |
As an antiatherogenic factor, heparinoid is thought to have a very important role in vivo, since AcylCoA acetyl transferase (ACAT) inmacrophages is inhibited by heparin. ACAT activity in diabetic macrophages was not inhibited by heparin. The 6keto-PGF1a, which is a stable metabolite of PGI2, was reduced in diabetic rats, macrophages. PGI2 attenuated heparin to inhibit ACAT through the activation of cholesteryl ester hydlase. Thromboxane A2 synthase inhibitor, ozagrel Na, inhibited the reesterification of cholesterol in diabetic rats. The inhibition of cyclooxiganase with acetylsalicylate decreased cholesterol reesterification in non-diabetic macrophages, but increased that in diabetic ones. On the other hand, the inhibitory effect of heparin for ACAT was enhanced by acetylsalicylate in rats with and without diabetes. Therefore, heparin is thought to have a direct inhibitory effect on ACAT,independent to prostaglandines. Oxidized LDL which is known to inhibit the synthesis of heparinoid induced the accumulation of cholesteryl ester in macrophages, which was inhibited by heparin. The synthesis of heparin seemed to be stimulated with prostacyclin. Therefore, heparinoid is thought to have an important role in the regulation of ACAT,and participates in the accumulation of cholesterol metabolism in macrophages.
|
