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2001: This is the beginning of the new theory !

2001: This is the beginning of the new theory !. Inflammation and Atherosclerosis, Libby, Ridker, Maseri, Circ., 2001, 105, 1135-1143 . o r P. Libby “ Atherosclerosis ” THE NEW VIEW, The Scientific American. May, 2002, 48-56.

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2001: This is the beginning of the new theory !

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  1. 2001: This is the beginning of the newtheory!

  2. Inflammation and Atherosclerosis, Libby, Ridker, Maseri, Circ., 2001, 105, 1135-1143 or P. Libby “Atherosclerosis” THE NEW VIEW, The Scientific American. May, 2002, 48-56

  3. The various stages of plaque development and when to interfere

  4. Normalvesselappearance Early plaque Obstructive plaque Plaque rupture Sequence of atheroscleroticprocess Plaques increase in number and size Unstable angina Endothelialdysfunctionbegins Acute myocardialinfarction - Cardiacfailure Non-invasive tests normal Invasive tests abnormal Level of vascularinflammation indicators (VCam, Ecam, MCP-1, MIF, IL-6, ox-LDL, CRP?) graduallyrising as severity of diseaseincreases So begin treatmentHERE! Suddendeath Adaptedfrom N. E.J. Med, 2004 Clinicallynon-detectable Clinically evident 10 20 40 ≥ 60 years

  5. In certainregions of France, goodfood and wine, elsewhere in Western World, Fastfood and sweetdrinks. It shows in longevity!

  6. The french paradoxwhat is the essential factor? • Jean vs. Joe

  7. 6glasses of a specific* red wine (~280ml) = 500 à 1000mg polyphenols are neededfordailydose • *) Château Petrus… = EXPENSIVE! • ` …or 2 capsules? IT IS YOUR CHOICE!

  8. Multiple mechanismsform a beneficial cascade

  9. Multiple mechanisms of action of polyphenols “THE BENEFICIAL CASCADE”VASCULAR RELAXATION (NO stimulation / endothelinreduction)+ANTI-INFLAMMATORY+ANTI-CHOLESTEROLEMIC+ ANTI-THROMBOTIC +ANTI-OXIDANT ACTION=Together: VASCULAR PROTECTIVE and ANTI-ATHEROSCLEROTIC

  10. Visuals of the variousprocessesinvolved in the initiation of anatherosclerotic plaque and where the polyphenols stop inflammation

  11. Rwpc’s and atherosclerosisPhases of leukocyte-endothelialinteraction II Leukocyte Chemoattractants of endothelial surface (V-cam, E-cam, MCP-1, MIF etc) Endothelium

  12. Rwpc’s and atherosclerosisPhases of leukocyte-endothelialinteraction III RWPC block MCP-1 and MIF and STOP inflammation HERE Leukocyte Recruitment Slow Rolling Endothelium So block MCP-1, MIF early... …instead of the mechanicalinterventions later

  13. STOP slow rolling beforetheyadhere! Rwpc’s and atherosclerosisPhases of leukocyte-endothelialinteraction IV Leukocyte Recruitment Slow Rolling Adhesion Endothelium So block MCP-1, MIF early... …instead of the mechanicalinterventions later

  14. Avoidbirth of a plaque! Rwpc’s and atherosclerosisPhases of leukocyte-endothelialinteraction V Leukocyte Recruitment Slow Rolling Adhesion Transmigration Endothelium Selectins MCP-1, MIF Integrins Cholesterol deposition Plaque development by other proinflammatory molecules

  15. Resveratrol, one of the polyphenolscanavoidlesiondevelopment as effective as atorvastatin

  16. The polyphenol Resveratrol protects against atherosclerosis in hyperlipidemicAPOE3-Leiden.CETP mice Control Resveratrol Atorvastatin + Resveratrol Atorvastatin Berbée JF et al. J. Nutr. Biochem. 2013;24(8):1423-1430

  17. Polyphenols* protect against atherosclerosis Berbée et al., accepted for publication December 2012 * This was tested with the polyphenol Resveratrol

  18. The proven effects of red winepolyphenolson the endothelium and smoothmusclecell

  19. Polyphenols ROS P Thrombin PI3K/Akt CA2+ PDGFAB Protectiveeffects of Polyphenolsonbloodvessels (Schini, 2009) ROS MT1- MMP P NO p38 EDHF T2 VEGF ENDOTHELIAL CELL SMOOTH MUSCLE CELL Vasodilation Vasoconstriction Platelet aggregation Pro- MMP-2 VEGF VEGF expression MMP-2 activity MMP-2 Endothelial dysfunction Angiogenesis ATHEROGENESIS

  20. And in tabularform…

  21. The Maincharacteristics PREVENTIVE AND PROINTEGRITY OF ENDOTHELIUM VIA↑NO Production↓ENDOTHELIN↓V.CAM, E.CAM↓ MCP-1↓ MIF↓ Interleukin 6↓CRP↓ LDL, via ↑ receptor + ↓oxidation↑HDL↑ANTIOXIDANT =PRIMARY PREVENTIONTHERAPEUTIC AND PLAQUE REGRESSION VIA↓ LDL oxidation↓ SMC migration↓ SMC proliferation↓ platelet aggregation↓ VGEF = PLAQUE REGRESSION + ↓ metalloproteinase – action = PLAQUE STABILISATION = SECUNDARY PREVENTION

  22. Foodsupplementsplay a significant rolenext to generallifestylechanges.

  23. A MULTIFACTORIAL DISEASE DESERVES A MULTIFACTORIAL SOLUTION Smoking / Inflammation / Dyslipidaemia / Hypertension / Dysglycaemia Proinflammatorycytokineswhichultimatelylead to atherosclerosis (e.g. Vcam, Ecam, MCP-1, MIF, IL-6, TNFα, CD40L, CRP) So No smoking, physical activity 5x week Red fruits, nuts, vegetables 600gr per day Oilyfish 3x week or 6:1 EPA/DHA Oliveoil 4 tblsp/day oroleuropein+hydroxyltyrosol Red wine 4 glassesdayor 500mgm In VinoVeritas And dark chocolate? Lipid core ‘Messenger’ cytokine IL-6 Fibrinogen, PAI-1 Triglyceridemia OX_LDL Atheroma C-reactiveprotein Endothelial Dysfunction So, strictlyadhere to the MediterraneanDietor supplement a varieddietwithfood medicines such as polyphenols and PUFA’s. EHJ 2010, Oxf. Univ. Press

  24. Let food be the medicine

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