1. Thrombus Susceptibility and the Vulnerable Plaque Relationship Between Inflammation and Thrombosis

2. VBWG Wagner DD. Arterioscler Thromb Vasc Biol. 2005;25:1321-4. Interaction between inflammation and hemostasis in vulnerable plaque

3. VBWG Harrison DG. Nat Med. 2005;11:375-6. Txnip = thioredoxin interacting protein (vitamin D upregulating protein 1) ASK = apoptosis-signaling kinase; JNK = Jun-terminal kinase Txnip links shear stress to inflammation No shear Txnip Thioredoxin inactive Normal shear Txnip Thioredoxin active

4. VBWG Freedman JE. Circulation. 2005;112:2725-34. ADP = adenosine diphosphate; NO = nitric oxide; R = platelet receptors; TXA 2 = thromboxane A 2 ; vWf = von Willebrand factor Disrupted endothelium GPIb-IX-V Active GP IIb/IIIa Fibrinogen TXA 2 ADP Inactive GP IIb/IIIa Unactivated platelet NO Subendothelial matrix Platelet adhesion and aggregation R R vWf

5. VBWG Chakrabarti S et al. Arterioscler Thromb Vasc Biol. 2005;25:2428-34. 0 5 10 sCD40L (ng/mL) 050100150200250300350 Time (minutes) + Thrombin – Thrombin Platelets release soluble CD40 ligand (sCD40L) after thrombin stimulation

6. VBWG Chakrabarti S. et al. Arterioscler Thromb Vasc Biol. 2005;25:2428-34. Recombinant sCD40L enhances platelet release of reactive oxygen species Platelets + Dihydrorhodamine UnstimulatedTRAPTRAP + rsCD40L TRAP = Thrombin receptor-activated platelets

7. VBWG André P et al. Circulation. 2002;106:896-9. Activated plateletUnstimulated platelet GP IIb/IIIa antagonists block sCD40L release from platelets

8. VBWG Curran MP, Keating GM. Drugs. 2005;65:2009-35. Thrombolytics Abciximab Tirofiban Eptifibatide UFH LMWHs Direct thrombin inhibitors Aspirin Thromboxane A 2 Collagen ADP Thrombin Fibrinogen Fibrin GP IIb/IIIa activation von Willebrand factor Platelet aggregation Thrombus formation Ticlopidine Clopidogrel Points of action for antithrombotics

9. VBWG GP IIb/IIIa + PCI ≥80% occupancy GP IIb/IIIa + No PCI 12 hours Antman EM. Am Heart J. 2003;146(suppl):S18-22. Proposed model for optimal use of GP IIb/IIIa inhibitors

10. VBWG Furman MI et al. J Thromb Haemost. 2005;3:312-20. Giugliano RP, Braunwald E. J Am Coll Cardiol. 2005;46:906-19. Potential mechanisms for reduction of thrombo- inflammation with GP IIb/IIIa inhibition Inhibit platelet activation Reduce sCD40L in ACS and PCI Blunt CRP increase in ACS and PCI Reverse endothelial dysfunction induced by PCI Reduce leukocyte-platelet aggregation in ACS