218 pharmacologic stabilization of vulnerable plaque
TRANSCRIPT
Pharmacologic Stabilization of Vulnerable Plaque: A Premature
Concept?
LDL
Ox LDL
Infection/inflammation
Homocysteine
Smoking
Endothelial release of MCP-1NO
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
Inflammation Coagulation
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
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)
Anti-inflammatory
AspirinNSAIDsCox-2 inhibitorsStatins
Triggers of Plaque RuptureAwakening Rx: AspirinExercise Anti-adrenergicsAnger Timing of Rx Fear (e.g., earthquake) CounselingSexual activity Sedatives?Fatty meal Anti- depressants? Cocaine, decongestants, marijuanaCold weatherPollutionMondays
Statins
SimvastatinAtorvastatinPravastatinFluvastatinLovastatinCerivastatinRosuvastatin
Anti-microbials
roxithromycin
azithromycingancicloviroseltamivirzanamivir
Future
Antioxidants α-tocopherol β-carotene Vitamin C Selenium Flavunoids Green tea N-acetyl cycteine Probucol Dietary fat reduction eNOS induction Statins
Antiplatelets and Antithrombotics
Aspirin, Ticlopidine, ClopidogrelHeparin, LMWHGPIIb/IIIa inhibitors
Antibodies (Abciximab)Synthetic antagonists (Eptifibatide, Tirofiban)
Thrombin Inhibitors (Argatroban,Hirudins)
Texas Heart Institute University of Texas-Houston
Center for Vulnerable Plaque Research