|Budget Amount *help
¥12,000,000 (Direct Cost : ¥12,000,000)
Fiscal Year 1999 : ¥6,800,000 (Direct Cost : ¥6,800,000)
Fiscal Year 1998 : ¥5,200,000 (Direct Cost : ¥5,200,000)
We have investigated in the signal transduction from thrombin receptor, PAR-1 and its role in the development in atherosclerosis/vascular remodeling and thrombosis.
We identified as follows:
1. The activation of PAR-1 by thrombin causes the expression of cell adhesion molecules(CAM), inflammatory cytokines, tissue factor, and PAI-1. This may play some roles in the development in atherosclerosis/vascular remodeling and thrombosis.
2.Thrombin activates PAR-1, and causes the activation of NF-ィイD2κィエD2B through MAP kinase pathway, resulting the proliferation of vascular smooth muscle cells.
3. On the other hand, PAR-1 activation causes apoptosis through caspase cascade.
4.Furthermore, we showed the signaling from PAR-1 activates histone acetyltransferase(HAT) with CBP/p300 activation in the cultured vascular smooth muscle cells. This causes accumulation of acetylated proteins at lysine residue, named as hyper-nuclear acetylation(HNA).
5. We showed HNA in atherosclerotic plaque in human cororary artery.
Based on these data, we conclude the signaling from thrombin receptor activates NF-ィイD2κィエD2B and CBP/p300 through MAP kinase cascade. This may cause proliferation, activation, and/or apoptosis in vascular smooth muslce cells, and play some roles for the development in vascular remodeling/restenosis and atherosclerosis/thrombosis.