Molecular mechanism on the progression of atherosclerosis.

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We are focussing on the atherogenesity of oxidized LDL,in particular lysophosphatidyl-choline (Lyso-PC) which generated in atherosclerotic lesions. Lyso-PC has been shown to differentially up regulate adhesion molecules, such as VCAM-1 and ICAM-1 expression and growth factors in various cultured cells, including endothelial cells, macrophages and T cells. In addition, INF-gamma and IL-2 receptor are induced by Lyso-PC in T cells.In case of PDGF-B chain and ICAM-1, induction of these molecules are independent of PMA-regulatable PKC activation but suppressed by increased level of intracellular cyclic AMP in cultured endothelial cells. In addition, induction of PDGF-B chain is required newly synthesized protein, probably transcriptional factor. Therefore we put forward on the signal transduction system of Lyso-PC,concerning the expression of ICAM-1 and PDGF-B chain collaboration with both Dr.Chait, Cybulsky and Gimbrone.We also investigated the sequential expression of P-selectin, VCAM-1, E-selectin, activated macrophages and T lymphocytes in and on the endothelial cellsby antibodies respectively, using cholesterol fed rabbits at the orifice of first branch of intercostal artery. At one week of cholesterol feeding, P-selectin and VCAM-1 are detected. And activated macrophages are observed in the same place at following 2 weeks. At three week after cholesterol-feeding, T-lymphocytes are detected at the same place and continued to be detected until 10 weeks. However E-selectin was not detected.