Mechanisms of cyclooxygenase2 expression-induced by oxidized-LDL in VSMC

• Project/Area Number: 13670736
• 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: Yokohama City University Hospital
• Principal Investigator: YAMAKAWA Tadashi Yokohama City University Hospital Instructor, 医学部附属病院, 助手 (30264641)
• Co-Investigator(Kenkyū-buntansha): KAWAMOTO Susumu Yokohama City University Dept of Bacteriology Assistant Professor, 医学部・細菌学, 講師 (80125921)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000); Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: Cyclooxygenase2 / p42 / 44MAPK / p38MAPK / Atherosclerosis / VSMC / cyclooxygenase2 / cyclooxygenase 2

Research Abstract

In 2001, proliferation of vascular smooth muscle cells (VSMC) were found to be mediated through cyclooxygenase 2 (COX2) expression-induced by Oxidized LDL. We also identified that COX2 expression was dependent on the activation of p42/44MAPK and p38MAPK. In 2002, in order to elucidate the regulation of transcription of COX2 and novel pathways besides MAPKs, we performed following experiments. First, we examined the role of p42/44MAPK and p38MAPK on cox2 mRNA expression. We identified that p42/44MAPK was related with transcription of cox2 and p38MAPK was associated with the stabilization of cox2 mRNA. Second, Dr Eguchi found that mRNA expression of helix-loop helix Id3 aw well as p21WAP/Cip1 and p27Kip1 were enhanced by oxidized-LDL stimulation in VSMC. It is very interesting that all of them were cell cycle related genes. Therefore, we need to do further investigation of the signaling pathway of these genes-induced by oxidized-LDL to identify the mechanisms of growth of VSMC.

Research Products

• [Publications] T Yamakawa et al.: "Lysophosphatidylcholine activates Extracellular Signal-Regulated Kinases 1/2"Arteriosclerosis, Thrombosis, and Vascular Biology. 22. 752-758 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T Yamakawa et al.: "Lysophosphatidylcholine Inhibits Insulin-Induced Akt Activation Through Protein"Hypertension. 39. 508-512 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T. Yamakawa et al.: "Lysophosphatidylcholine activates Extracellular Signal-Regulated Kinesis 1/2 through Reactive Oxygen Species in Rat Vascular Smooth Muscle Cells"Arteriosclerosis, Thrombosis, and Vascular Biology 22. 752-758 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Yamakasa et al.: "Insulin-Induced Akt Activation Through Protein Kinase C-α in Vascular Smooth Muscle Cells"Hypertension 39. 508-512 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Y Yamakawa et al.: "Lysophosphatidylcholine activates Extracellular Signal-Regulated Kinases 1/2 through"Arteriosclerosis, Thrombosis, and Vascular Biology. 22. 752-758 (2002)
• [Publications] T Yamakawa et al.: "Lysophosphatidylcholine Inhibits Insulin-Induced Akt Activation Through Protein Kinase C-in Vascular Smooth Muscle Cells"Hypertension. 39. 508-512 (2002)
• [Publications] T Yamakawa et al.: "Lysophosphatidylcholine activates Extracellular Signal-Regulated Kinases 1/2 through Reactive Oxygen Species in Rat Vascular Smooth Muscle Cells"Arteriosclerosis, Thrombosis, and Vascular Biology. (in press).