1995 Fiscal Year Final Research Report Summary
Regulation of VCAM-1 and ICAM-1 expression in atherogenesis
| Project/Area Number |
06671022
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KUME Noriaki Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (20252455)
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| Co-Investigator(Kenkyū-buntansha) |
YOKODE Masayuki Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (20252447)
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| Project Period (FY) |
1994 – 1995
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| Keywords | atherosclerosis / endothelium / adhesion molecules / growth factors / lysophosphatidylcholine / oxidized LDL / cyclic AMP |
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| Research Abstract |
Endothelial expression of mononuclear leukocyte adhesion molecules, such as VCAM-1, and ICAM-1, has been implicated in molecular mechanism involved in the recruitment of blood monocytes and lymphocytes into early atherosclerotic lesions. In the advanced lesions, migration and proliferation of medial smooth muscle cells into arterial intima are observed, and endothelial production of growth factors directed to smooth muscle cells appears to play a role in this process. We have identified lysophosphatidylcholine, a phospholipid component of atherogenic lipoproteins, such as oxidized LDL and beta-VLDL, as a candidate to activate endothelium to induce expression of adhesion molecules and growth factors, including VCAM-, ICAM-1, PDGF-A and -B chains and HB-EGF.In this research project, we have explored the signal transduction and transcriptional regulatory mechanisms responsible for lyso-PC-induced gene expression in cultured vascular endothelial cells. Our study revealed that activation of protein kinase C does not appear to be involved in lyso-PC-induced endothelial PDGF and ICAM-1 expression ; however, elevated levels of intracellular cyclic AMP inhibited the effect of lyso-PC.We have also found that certain protein can be rapidly tyrosine phosphorylated in response to activation with lyso-PC.Regarding to the transcriptional regulation by lyso-PC,our gel shift assays showed that lyso-PC did not activate NFkappaB but timedependently activate AP-1 to some extent.
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Research Products
(6 results)
