Involvement of thrombin/thrombin receptor signaling in the development of vascular remodeling

我们已经投资在thrombin receptor signal transductionpar1 and its role in the development in atherosclerosis/vascular remodeling and thrombosis.Weidentified as follows:1. The activation of par1 by thrombin causes The expression of cell adhesionmolecules(CAM), inflammatory cytokines, tissue factorand PAI-1. This may play some roles in the development in atherosclerosis/vascular remodeling andthrombosis.2.Thrombin activates par1，and causes the activation of NF- D2κ D2B through MAP kinase pathway，resulting the proliferation of vascular smooth muscle cells.3. On the other hand，par1 activation causes apoptosis through caspase cascade.4.Furthermore，we showed the signaling from par1 activates histone acetyltransferase(HAT) with CBP/p300 activationin the cultured vascular smooth muscle cells. This causes accumulation of acetylated proteins atlysine residue,5.我们应该在人类cororary中的atherosclerotic plaque in human cororary （HNA）我们应该在atherosclerotic plaque in human cororaryartery.Based on these data，我们conclude the signaling from thrombin receptor activates f - D2κ D2B and CBP/p300 through MAPkinase cascade. This may cause proliferation, activationand/or apoptosis in vascular smooth muslce cells，and play some roles for the development in vascular remodeling/restenosis andatherosclerosis / thrombosis。

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.