1. Introduction
2. Galen discovered blood travels in arteries and veins
3. Reasons to think about vascular disease
4. The inert vessel wall...
5. Quiescent vs. active epithelial layer
6. Questions
7. Outline
8. Coagulation pathway
9. Discovery of protein C (PC)
10. Protein C (PC)
11. Structure of PC
12. Extrahepatic sites of PC synthesis
13. Major players: TM, PF4, EPCR, thrombin, PC
14. Thrombomodulin (TM) and protein C activation
15. APC promotes fibrinolysis
16. PC activation and clearance of APC
17. Physiologic importance of PC (1)
18. Physiologic importance of PC (2)
19. Resistance to APC: factor VLeiden
20. Factor VLeiden
21. Benefits of factor VLeiden
22. The PC-TM system and inflammation (1)
23. The PC-TM system and inflammation (2)
24. Anti-inflammatory properties of APC
25. Anti-inflammatory properties of APC-EPCR
26. Vasculoprotective properties of APC-EPCR
27. Therapeutic importance of APC
28. APC versus PC
29. Thrombomodulin and the TAFI
30. TM and role of C-type lectin-like domains
31. Deletion of the lectin-like domain of TM
32. Increased sensitivity of TMLed/Led mice to LPS
33. Higher serum cytokines in TMLed/Led mice
34. Increased PMN accumulation in TMLed/Led lungs
35. More myocardial infracts after ischemia-reperfusion
36. Increased PMN adhesion to TMLed/Led ECs
37. ICAM, VCAM and pERK1/2 endothelial cells
38. Soluble thrombomodulin (sTM)
39. TMLec155 suppresses leukocyte adhesion
40. TMLec155 suppresses activation of ERK1/2
41. Co-ordinate action of TM and APC-EPCR
42. HMGB1 - high mobility group box 1
43. N-terminal domain of TM: inhibitor of HMGB1
44. Summary of role of TM in inflammation
45. Role of TM in cancer
46. Regulation of TM
47. Regulation of EPCR
48. TM and proteinase activated receptors
49. TM mutations and disease
50. PC-TM system in development
51. PC-TM mechanism - in feto-maternal interface
52. Pulling it together...
53. Local response to injury
54. Protection of adjacent tissue
55. Future directions
56. Therapeutics of PC/APC
57. Therapeutics of EPCR
58. Therapeutics of thrombomodulin
59. Diagnostic insights
60. Potential impact
61. We need to do more research
62. END