Schermuly PVRI China 英文版 医学资料.ppt

* Die benigne Proliferation von Zellen in Gef??w?nden und Atemwegen spielt eine wesentliche Rolle bei kardiopulmonalen Erkrankungen wie Artherosklerose, Restenose, Schlaganfall, Hypertonie oder chronisch obstruktiven Lungenerkrankungen. * * * * * * * * New molecular targets in preclinical development for PAH The present - Vasodilator Therapy Major signaling pathways are currently addressed Prostanoids (Iloprost, Prosta- cyclin, Beraprost, Treprostinil) ETA/B i (Bosentan) and ETA i (Sitaxsentan, Ambrisentan) PDE5 i (Sildenafil, Tadalafil) Remodeling: (pseudo)malignant disease? Apoptosis Endothelium Fibroblasts Proliferation Inflammatory Cells Migration Myocytes How to target remodeling? Mediators / Receptors Prostanoids, Serotonin-Antagonists Endothelin-Antagonists Channel Blocker Growth Factor Antagonists neutralizing antibodies Intracellular Signaling / Transcription factors siRNA, antisense Strategies MAP kinase inhibitors PDE- Inhibitors sGC stimulators raf / ras inhibitors ROS, NADPH-Ox. Effectors Elastases MMP, Chymases Survivin cyclin-dependent kinases (cdk) New compounds Non vasactive anti-proliferative drugs: tyrosine kinase i, elastase i New vasodilators: sGC activators, Rho-kinase i, serotonin antagonists Apoptosis induction (dichloroacetate DCA; survivin inhibition) Stem cells, endothelial progentior cells, gene transfer, siRNA How to target remodeling? Mediators / Receptors Prostanoids, Serotonin-Antagonists Endothelin-Antagonists Channel Blocker Growth Factor Antagonists neutralizing antibodies Intracellular Signaling / Transcription factors siRNA, antisense Strategies MAP kinase inhibitors PDE- Inhibitors sGC stimulators raf / ras inhibitors ROS, NADPH-Ox. Effectors Elastases MMP, Chymases Survivin cyclin-dependent kinases (cdk) Protein Tyrosine Kinases ~100 Protein tyrosine kinases 59 receptor tyrosine kinases (RTK) 32 non-receptor tyrosine kinases regulate key cell functions such as proliferation, differentiation, anti-apoptotic s