SHAPE Society

1. Pharmacologic Stabilization of
Vulnerable Plaque: A Premature
Concept?

2. LDL
Ox LDL
Infection/inflammation
Homocysteine
Smoking
Endothelial release of MCP-1
NO
PGI2
HSPG
 tPA
Tm
ICAM 1
VCAM 1
TSP
TNF α
IL 1
PAI1
MONOCYTE:
Chemo-attraction (MCP 1)
Attachment(LFA1, Mac1,etc)
Attraction (NFκB)
Proliferation (TNF α,MCSF)
Secretion of TNF α , IL-1, MCP-1, NO
T cell activation (CD 40)
Inhibition of SMC metabolism Activation of MMPs
Apoptosis of SMC Activation of acid proteases
Angiogenesis
Diet low in antioxidants
Low HDL
A-II

3. Inflammation Coagulation

8. Pharmacologic Stabilization of
Vulnerable Plaque
 Anti-inflammatory agents (aspirin, Plavix, etc)
 Antiplatelets
 Anticoagulants
 Antiplatelets
 Anti-microbials
 Lipid-lowering agents
 Antioxidants
 Beta blockers
 Angiogenesis inhibitors (endostatin, α VEGF)
 eNOS inductors

9. Pharmacologic Stabilization of
Vulnerable Plaque, contd.
 ACE inhibitors
 MMP inhibitors
 Vasodilators (amlodipine, TNG)
 Apo A1 Milano, HDL
 TF inhibitors
 CETP inhibitors
 Cytokines antagonists (selectins, ICAM, VCAM,
NFκB, TGF-ß, MCP-1, TNF-α, PDGF)
 Retinoids (retinoic acid, TGF-ß)
 Antibodies to CD40 ligand
 Cap strengthening (TGF -ß, antibody to IF γ)

10. Anti-inflammatory
Aspirin
NSAIDs
Cox-2 inhibitors
Statins

11. Triggers of Plaque Rupture
Awakening Rx: Aspirin
Exercise Anti-adrenergics
Anger Timing of Rx
Fear (e.g., earthquake) Counseling
Sexual activity Sedatives?
Fatty meal Anti- depressants?
Cocaine, decongestants, marijuana
Cold weather
Pollution
Mondays

12. Statins
Simvastatin
Atorvastatin
Pravastatin
Fluvastatin
Lovastatin
Cerivastatin
Rosuvastatin

13. Anti-microbials
roxithromycin
azithromycin
ganciclovir
oseltamivir
zanamivir
Future

14. Antioxidants
 α-tocopherol
 β-carotene
 Vitamin C
 Selenium
 Flavunoids
 Green tea
 N-acetyl cycteine
 Probucol
 Dietary fat reduction
 eNOS induction
 Statins

15. Antiplatelets and Antithrombotics
Aspirin, Ticlopidine, Clopidogrel
Heparin, LMWH
GPIIb/IIIa inhibitors
Antibodies (Abciximab)
Synthetic antagonists (Eptifibatide, Tirofiban)
Thrombin Inhibitors (Argatroban,Hirudins)

16. Texas Heart Institute University of Texas-Houston
Center for Vulnerable Plaque Research