Involvement of WSX-1 in atherosclerosis

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590748
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Saga University
• Principal Investigator: HIRASE Tetsuaki Saga University, Faculty of Medicine, Instructor (60363446)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Hiroki Saga University, Faculty of Medicine, Professor (40260715) ; AKASHI Makoto Saga University, Faculty of Medicine, Lecturer (30398119) ; INOUE Teruo Saga University, Faculty of Medicine, Associate Professor (20168454) ; NODE Koichi Saga University, Faculty of Medicine, Professor (80359950)
• Project Period (FY): 2005 – 2006
• Keywords: cardiovascular disease / atherosclerosis / inflammation / cvtokine

Research Abstract

Atherosclerosis is a chronic inflammatory disease. It has been shown that cytokines play important roles in vascular inflammation in atherosclerosis. IL-27 that is a member of IL-12 family regulates Th1 cell differentiation and production of inflammatory cytokines from T cells. In this study, we aimed to examine the involvement of EBI3, a component of IL-27, and WSX-1, a component of IL-27 receptor, in atherosclerosis.
We crossed EBI3 knockout mice and WSX-1 knockout mice with atherosclerosis-prone LDL receptor knockout mice to generate double knockout mice. LDL receptor knockout mice and double knockout mice were fed with high cholesterol diet for 16 weeks from the age of 8 weeks old. Body weight, blood pressure and serum cholesterol levels showed no significant differences among LDL receptor knockout mice and double knockout mice. Atherosclerotic lesions in aorta stained with oil red O were larger in double knockout mice than in LDL receptor knockout mice. Areas stained with MOMA-2, a macrophage marker, in atherosclerotic lesions were larger in double knockout mice than in LDL receptor knockout mice.
These data suggest that deficiency of EBI3 and WSX-1 promotes atherosclerosis through macrophage activation. Further studies are necessary to elucidate the molecular mechanisms responsible for macrophage activation in deficiency of EBI3 and WSX-1.

Research Products

• [Journal Article] 動脈硬化予防ガイドライン2007年版からみた脂質異常症のと.らえ方と治療方針(6) (2008)
  • Author(s): 平瀬 徹明, 野出 孝一
  • Journal Title: 薬局 59・2 Pages: 200-203
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A guideline for the treatment of dyslipidemia (2008)
  • Author(s): Tetsuaki Hirase, Koichi node
  • Journal Title: The Journal of Practical Pharmacy 59 Pages: 200-203
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Xenogenic macrophage immunization reduces atherosclerosis in apolipoprotein E knockout mice (2007)
  • Author(s): Yamashita T, Kawashima S, Hirase T, Shinohara M, Takaya T, Sasaki N, Takeda M, Tawa H, Inoue N, Hirata K, Yokoyama M.
  • Journal Title: American Journal of Physiology 293 Pages: C865-873
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Xenogenic macrophage immunization reduces atherosclerosis in apolipoprotein E knockout mice. (2007)
  • Author(s): Yamashita T, Kawashima S, Hirase T, Rhinohara M, Takaya T, Sasaki N, Takeda M, Tawa H, Inoue N, Hirata K, Yokoyama M.
  • Journal Title: American Journal of Physiology 293 Pages: C865-873
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Simvastatin stimulates vascular endothelial growth factor production by hypoxia-inducible factor-1α up-regulation in endothelial cells
  • Author(s): Ai Nishimoto-Hazuku, Tetsuaki Hirase, Noriko Ide, Yuji Ikeda, Koichi Node
  • Journal Title: Journal of Cardiovascular Pharmacology (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Angiotensin II Increases the Expression of IP-10 and Renin-angiotensin System in Endothelial Cells
  • Author(s): Noriko Ide, Tetsuaki Hirase, Ai Nishimoto-Hazuku, Yuji Ikeda, Koichi Node
  • Journal Title: Hypertension Research (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Simvastatin stimulates vascular endothelial growth factor production by hypoxia-inducihle factor-la up-regulation in endothelial cells.
  • Author(s): Ai Nishimoto-Hazuku, Tetsuaki Hirase, Noriko Ide, Yuji Ikeda, Koichi Node
  • Journal Title: Journal of Cardiovascular Pharmacology (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Angiotensin II Increases the Expression of IP-l0 and Renin-angiotensin System in Endothelial Cells.
  • Author(s): Noriko Ide, Tetsuaki Hirase, Al Nishimoto-Hazuku, Yuji Ikeda, Koichi Node
  • Journal Title: Hypertension Research (in press)
  • Description: 「研究成果報告書概要(欧文)」より