2003 Fiscal Year Final Research Report Summary
Study on the mechanism of atherosclerotic lesion formation using cytokine-knockout mouse
| Project/Area Number |
13470517
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Laboratory medicine
|
|---|
| Research Institution | Gifu University |
|---|
Principal Investigator |
SEISHIMA Mitsuru Gifu University, School of Medicine, Professor, 医学部, 教授 (10171315)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJII Hidehiko Gifu University, School of Medicine, Research Associate, 医学部, 助手 (50301213)
WADA Hisayasu Gifu University, Hospital, Assistant Professor, 医学部附属病院, 講師 (10283300)
|
|---|
| Project Period (FY) |
2001 – 2003
|
| Keywords | Cytokine / Atherosclerosis / Bone marrow transplantation / Knockout mouse |
|---|
| Research Abstract |
1.In the study on the comparison of TNF-α^<-/-> apoE^<-/-> double KO mouse with apoE^<-/-> KO mice, the area of atherosclerotic lesion was significantly reduced in double KO mice. In addition, the expression of adhesion molecules such as ICAM-1and VCAM-1was also significantly suppressed in double KO mouse. These fidings suggest that augumented expression of adhesion molecules is, at least in part, involved in the atherosclerotic action of TNF-α.
2.The atherosclerotic lesion was significantly reduced in IFN-γ^<-/-> apoE^<-/-> double KO mice compared with apoE^<-/-> KO mice and mRNA levels of ICAM-1 and VCAM-1 were significantly decreased in double KO mice. It is suggested that mononuclear cells including monocytes are recruited to arterial wall by IL-1β, resulting in the formation of atherosclerotic lesion.
3.The atherosclerotic lesions of IFN-γ^<-/->BMT mice were larger than those of IFN-γ^<+/+>BMT mice at the aortic sinus, aortic arch and abdominal aorta. These findings show that IFN-γ produced by bone marrow-derived cells delays the progression of atherosclerosis without any effects on plasma lipids, and this suppression may be due to decreased extracellular matrix deposition.
In this study, we clarified that TNF-α and IL-1β accelerate atherosclerosis via the augumented expression of adhesion molecules in vivo study. However, IFN-y derived from bone marrow rather suppressed atherosclerosis at least in the initial stage.
|
