| Co-Investigator(Kenkyū-buntansha) |
ISHII Kenji KYOTO UNIVERSITY,GRADUATE SCHOOL OF MEDICINE,INSTRUCTOR, 医学研究科, 助手 (00212811)
KUME Noriaki KYOTO UNIVERSITY,GRADUATE SCHOOL OF MEDICINE,INSTRUCTOR, 医学研究科, 助手 (20252455)
YOKODE Masayuki KYOTO UNIVERSITY,GRADUATE SCHOOL OF MEDICINE,LECTURER, 医学研究科, 講師 (20252447)
DOI Toshio KYOTO UNIVERSITY,GRADUATE SCHOOL OF MEDICINE,LECTURER, 医学研究科, 講師 (60183498)
MURAKAMI Motonobu KYOTO UNIVERSITY,GRADUATE SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学研究科, 助教授 (10157761)
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| Research Abstract |
Vascular endothelial cells, at early stage of atherosclerosis, plays a pivotal role, expressing endothelial leukocytes adhesion molecules (ICAM-1, VCAM-1) , growth factors (HB-EGF,PDGF-A,B chain) and cytokines in response to various pathophysiological stimuli. We have found that lysophosphatidyl-choline (Lyso-PC) , a prominent phospholipid component of atherogenic lipoproteins, such as oxidized LDL,upregulated differentially VCAM-1 and ICAM-1 expression in various cultured endothelial cells. In addition Lyso-PC has been demonstrated to induce gene expression of potent smooth muscle growth factors such as PDGF-A and B chain, and HB-EGF in cultured human endothelial cells. We are now trying to identify some proteins which are phosphorylated by the stimulation of Lyso-PC and verify the signal transduction pathway for Lyso-PC reactions in vascular endothelial cells. We also examined the expression of adhesion molecules and blood cells (such as monocyte-macrophages, T lymphocytes) in the atherosclerotic lesions in vivo, using WHHL-rabbits and cholesterol fed rabbits by immunological methods. At very early stage, around one P selectin molecules are expressed. At 3 week, we found that activated macrophages and after one more week T lymphocytes are identified at same lesions as adhesion molecules are expressed. Finally we found Lyso-PC could induce some growth factors and cytokines in T lymphocytes. We are now studying the molecular mechanisms of Lyso-PC actions to endothelial cells and T-lymphocytes.
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