| Project/Area Number |
11557055
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Osaka University Graduate School of Medicine |
|---|
Principal Investigator |
YAMASHITA Shizuya Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (60243242)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAKAI Naohiko Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80294073)
NAKAMURA Tadashi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90252668)
TOMIYAMA Yoshiaki Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80252667)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1999: ¥6,800,000 (Direct Cost: ¥6,800,000)
|
|---|
| Keywords | Oxidized LDL / Receptor / Atherosclerosis / CD36 / Long-chain fatty acid / Scavenger receptor / 酸化LDL受容体 / 動脈硬化 / トランスジェニックマウス |
|---|
| Research Abstract |
CD36 is an 88 kDa membrane glycoprotein and is expressed on platelets, monocytes, monocyte-derived macrophages and adipose tissues. CD36 was reported to be a receptor for collagen and thrombospondin as well as a transporter of long-chain fatty acids. We have identified patients with CD36 deficiency and reported 3 novel mutations in the CD36 gene. We also found that CD36 is a receptor for oxidized LDL, using monocyte-derived macrophages from CD36-deficient subjects and that CD36 is expressed on foamed macrophages in the human atherosclerotic aorta and coronary arteries. In the current study, we tried to establish polyclonal antibodies that block CD36 and also to develop CD36 knockout mice by genetic engineering technique. We have obtained ES cells with a homologous recombination and are currently trying to obtain chimera mice by microinjection to examine the effect of CD36 knockout on the development of atherosclerosis in apo E or LDL receptor knockout mice. We have so far identified 26 CD36-deficient subjects, all of whom showed a complete deficiency of myocardial uptake of ^<123>I-BMIPP, a long-chain fatty acid analogue. It is noteworthy that the CD36-deficient patients were accompanied by hyperlipidemia (especially hypertriglyceridemia), an increase in remnant lipoproteins and a slight elevation of blood pressure. These subjects were also accompanied by insulin resistance and multiple risk factors. Thus, deficiency of CD36 may be one of the genetic causes of multiple risk factor syndrome possibly through insulin resistance. The mechanism for the insulin resistance in patients with CD36 deficency is currently underway.
|
