Studies for the Mechanisms of oxidized LDL-induced growth in vascular smooth muscle cells

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590764
• 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
• Principal Investigator: YAMAKAWA Tadashi Yokohama City University, 医学部附属病院, Associate Professor (30264641)
• Co-Investigator(Kenkyū-buntansha): TANAKA Shunichi International University of health and welfare, Professor (40236592)
• Project Period (FY): 2003 – 2005
• Keywords: Oxidized LDL / vascular smooth muscle / Id3

Research Abstract

Several lines of evidence have suggested that oxidatively modified LDL plays a key role in atherogenesis. The mechanisms of atherogenesis by oxidized LDL remains unknown. Therefore, we totally investigated all expressed genes induced by the stimulation with oxidized LDL by using DNA chip analysis. It was found that helix-loop-helix Id3 (Id3) mRNA expression was enhanced and CDK-inhibitor, p21WAF/Cipl and p27Kipl expression were decreased by oxidized LDL stimulation.
We constructed Id3 promotoro/luciferase chimera plasmid and then analyzed oxidized LDL-induced luciferase activity. Pretreatment of Actinomycin D, oxidized LDL induced Id3 mRNA expression was enhanced suggesting that the mechanisms of Id3 expression might be increased transcription and mRNA stability.
Id3 mRNA expression was inhibited with SB203580, p38 MAPK inhibitors, or dominant negative mutant of p38MAPK expression.
In conclusion, VSMC growth by oxidized LDL is crossly associated with cell cycle related protein, helix-loop-helix Id3, however, detailed mechanisms are necessary to do further investigation.