This document discusses platelet physiology and the role of platelets in cardiovascular disease. It covers several topics: 1) Inside-out and outside-in integrin signaling pathways that are important for platelet activation and aggregation. 2) Key signaling molecules and pathways involved in platelet activation in response to agonists like thrombin and collagen. 3) The role of calcium signaling and proteins like CIB1 in platelet spreading and clot retraction. 4) The function of JAM-A in platelet activation and clot retraction. 5) Storage conditions for platelets and common anti-platelet drugs used to control cardiovascular disease.

1. BISC 675 Cardiovascular Physiology Platelets 2 Ulhas P. Naik, Ph.D Professor and Director Delaware Cardiovascular Research Center

3. Intracellular Calcium

4. GPVI (Collagen Receptor) Signaling

5. Gq PLC  Ca 2+ G  i  P2Y12 -Adenylyl cyclase cAMP ADP Shape Change PI3K  Akt Rap1b Fibrinogen Receptor Activation, Platelet Aggregation, Secretion and Thromboxane Generation ? ? Indirect role Rho Kinase activation PKC Src tyrosine kinase AR-C69931MX MRS2179 Erk1/2 ? RhoA p160ROCK P2Y1, PAR1/4 TP  TRAP, TXA2 G 12/13 YM254890

6. Thrombin Signaling

7. Platelet Secretion

8. Integrin Inside-out Signaling

9. Integrin Outside-in Signaling

10. Events Leading to Platelet Aggregation

12. Platelet Aggregate Stabilization

13. Calcium- and Integrin-binding Protein 1

14. CIB1 in Platelet Spreading Discoid Spiky Partially spread Spread

15. CIB1 is Needed for Lamellipodia Formation -DMSO Anti-CIB1 cIgG +DMSO

16. CIB1 Deletion Affects Platelet Spreading on Immobilized Fibrinogen

17. Ablation of CIB1 Results in Delayed Clot Retraction

19. Ablation of JAM-A Results in Faster Clot Retraction

20. JAM-A movie

22. Anti-Platelet Drugs

23. Aspirin Aspirin inhibits both COX-1 and COX-2 Inhibition is 170 fold greater for COX1 Platelet express COX1 more than COX2

24. Anti-ADP Receptors

25.  IIb  3 Antagonists

26. Anti-platelet Therapy

27. Controlling Cardiovascular Disease Through Platelets