动脉硬化血栓病理生理学.ppt

Thrombin Serotonin Epinephrine Collagen ADP Activation TXA2 Activated Platelet COX Degranulation Aspirin ? ? Gp IIb/IIIa fibrinogen receptor To neighboring platelet Clopidogrel Ticlopidine Platelet agonists ADP ATP serotonin calcium magnesium Adhesive proteins thrombospondin fibrinogen p-selectin vWF Coagulation factors factor V factor XI PAI-1 Inflammatory factors platelet factor 4 CD 154 (CD 40 ligand) PDGF IV Gp IIb/IIIa Inhibitors TXA, thromboxane; PDGF, platelet-derived growth factor. Platelet Hyperreactivity Following ACS Predicts 5-Year Outcomes Platelet Aggregability Status 0 10 20 30 40 50 Death Cardiac Events 10.3 6.4 14.9 24.1 46.2 34.6 Patients (%) *RR=1.6 (CI 0.5-5.5) Negative (n=94) *RR=1.6 (CI 0.7-3.5) *RR=5.4 (CI 2.2-13.4) *RR=3.1 (CI 1.6-5.8) Intermediate (n=29) Positive (n=26) ACS, acute coronary syndrome. * Relative risk compared to group with negative aggregation. Adapted from Trip MD, et al. N Engl J Med. 1990;322:1549-1554. Platelets Release Inflammatory Mediators and Lead to Vascular Inflammation and Plaque Instability RANTES (Regulated on Activation, Normal T-cell?Expressed and Secreted). Libby P, et al. Circulation. 2001;103:1718-1720. Inflammatory Modulators CD 40 ligand Platelet factor 4 RANTES Unstable Plaque ActivatedPlatelets PlaqueRupture Thrombosis Thrombospondin Platelet-derived growth factor Nitric oxide CD40L is activated by agonists such as ADP, thrombin, or collagen. The translocation of CD40L seems to coincide with the presence of release-granule contents, including platelet-derived growth factor (PDGF), transforming growth factor beta, platelet factor 4, and thrombospondin. GP IIb/IIIa antagonists block the hydrolysis and subsequent release of SCD40L from platelets. The Shedding of Soluble SCD40L During Platelet Stimulation SCD40L, SCD40 ligand; PDGF, platelet-derived growth factor; TGF-?, transforming growth factor-beta; PF4, platelet factor 4; TSP,thrombospondin. Andre P, et al. Circulation. 2002:106:896-899. (wi