Summary of Research Project Results under JSPS FY2001
"Research for the Future Program"

1.Research Institution The University of Tokyo
2.Research Area Life Sciences
3.Research Field Genetic and Environmental Factors in Diseases Prevalent in Adults and the Elderly:Molecular and Cellular Mechanism of Vascular Complications
4.Term of Project FY 1997 〜 FY 2001
5.Project Number 97L00802
6.Title of Project A Role for Scavenger Receptor Pathway in the Pathogenesis of Vascular Disordes

7.Project Leader
Name Institution,Department Title of Position
Tatsuhiko Kodama The University of Tokyo, Research Center for Advanced Science and Technology Professor

8.Core Members

Names Institution,Department Title of Position
Takao Hamakubo The University of Tokyo, Research Center for Advanced Science and Technology Associate Professor
Noriko Noguchi The University of Tokyo, Research Center for Advanced Science and Technology Associate Professor
Takefumi Doi Osaka University, Graduate School of Pharmaceutical Sciences Professor

9.Summary of Research Results

1. Characterization of blood vessels in various organs
  We have developed principle method for the cultivation of endothelial cell from aorta, coronary artery and brain vessel. This method enabled us to organize coculture system and transcriptome analysis.
2. Moleculat mechanism of lipid accumulation in vascular wall cells
  We have developed a co-culture system for the analysis of lipid accumulation in arterial wall cells. Hypoxia and LDL overload can induce the lipid accumulation, and during this process, the expression of leptin, adipophilin, and CL100 genes are induced.
3. Molecular mechanism of endothelial upregulation of adhesion molecule
  Upregulation of adhesion molecule plays a critical role for the accumulation of monocytes to the atherosclerotic lesion. We identified a novel GATA pathway mediating this process, which can be an important target for the therapeutic drugs.
4. Transriptome analysis of blood vessel cells. RNA expression profile was studied during the activation of endothelial cells, hypoxia and cholesterol overload in smooth muscle cell and monocyte macrophage differentiation. The mechanism regulating these transcriptional activation has been studied.
5. Regulation of cholesterol metabolism in blood vessel cells.
  Proteases involved in the proteolysis of SREBP have been studied. We developed the method for the expression of SREBP/SCAP complex on the budded type baculovirus.
6. Development of novel therapeutics for the treatment of atherosclerosis
  We developed the novel anti-atherogenic antioxidant BO653. We have also analyzed the molecular mechanism of efficacy of novel statin, NK104 and novel GATA inhibitor, K7174 and related compounds.

10.Key Words

(1)Atherosclerosis、(2)Scavenger receptor、(3)Cholesterol
(4)Foam cell、(5)Endothelial cell、(6)Smooth mucle cell
(7)Macrophage、(8)Transcriptome、(9)Coculture system