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Pharmacologic treatment of vulnerable plaque
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
4.
5.
6.
7.
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
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