This document discusses potential pharmacologic approaches to stabilizing vulnerable plaque. It lists various categories of drugs that may help stabilize plaque, including anti-inflammatory agents, antioxidants, lipid-lowering agents, antiplatelets, anticoagulants, anti-microbials, and drugs that target specific biological processes in plaque development like angiogenesis and MMP inhibition. The document provides examples of specific drugs within each category that have been or could be studied for plaque stabilization, such as aspirin, statins, antibiotics, vitamins C and E, and MMP inhibitors. It also discusses non-pharmacologic triggers of plaque rupture that could potentially be addressed.

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