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Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma intramurale maturo complicanze rottura cappa fibrosa.

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Presentazione sul tema: "Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma intramurale maturo complicanze rottura cappa fibrosa."— Transcript della presentazione:

1 Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma intramurale maturo complicanze rottura cappa fibrosa placca fibrosa/ calcifica erosione endoteliale STENOSITROMBOSITROMBOSIRIMODELLAMENTO

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3 Rex A. Parker et al, The Journal of Biological Chemistry 1993;Nov. 6: Tocotrienol decrease incorporation of acetate but not mevalonate into cholesterol in HepG2 cells

4 Rex A. Parker et al, The Journal of Biological Chemistry 1993;Nov. 6: Suppression of HMG-CoA reductase total activity correlates with inhibition of cholesterol synthesis by -tocotrienol in HepG2 cells

5 A. Theriault et al., Clinical Biochemistry 1999;Vol 32: Mechanism of the cholesterol suppressive action of tocotrienol +--

6 A. Theriault et al., Clinical Biochemistry 1999;Vol 32: Mechanism for the reduction in low density lipoprotein (LDL) by tocotrienol

7 Asaf A. Qureshi et al., Atherosclerosis 2002;161: Effects of of Tocotrienol-Rich Fraction (TRF 25 ) on serum lipid parameters in hypercolesterolemic human subjects

8 Asaf A. Qureshi et al., Journal of Nutritional Biochemistry 2001;12: Synergistic effect of of Tocotrienol-Rich Fraction (TRF 25 ) and lovastatin

9 Asaf A. Qureshi et al., Journal of Nutritional Biochemistry 2001;12: Serum lipid parameters in GROUP A

10 Asaf A. Qureshi et al., Journal of Nutritional Biochemistry 2001;12: Serum lipid parameters in GROUP B

11 Formazione della Placca Aterosclerotica Attivazione endoteliale up-regulation molecole di adesione migrazione leucocitaria aumentata permeabilità endoteliale Shear stress intermittente F.di R. LDL Molecole di Adesione Selectine Immunoglobuline endoteliali Chemoattrattanti Chemochine Infiammazione

12 INTIMA E-selectina Matrice extracellulare Endotelio attivato VCAM-1 ICAM-1 ADESIONE MCP-1 M-CSF DIAPEDESI PECAM-1 Chemoattrattanti Chemochine MONOCITI Il legame del monocita allendotelio Selectine Immunoglobuline endoteliali (monocyte-chemoattractant protein-1) (macrophage colony-stimulating factor) (platelet endothelial-cell adhesion molecule-1)

13 formazione strie lipidiche migrazione cellule muscolari lisce ingrandimento nucleo lipidico LDL Fattori di Crescita Grow Factors Formazione della Placca Aterosclerotica lesione intermedia Infiammazione

14 Formazione della Placca Aterosclerotica Enzimi litici – Fattori della Coagulazione Metalloproteinasi lesione avanzata Infiammazione assottigliamento del cappuccio fibroso (erosione) rottura della placca (shoulder region) TROMBOSI F.di R. LDL Fattore Tissutale

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19 A. Theriault et al., Atherosclerosis 2002;160:21-30 Concentration dependent effects of -Tocotrienol on VCAM-1 expression in cultured endothelial cells

20 A. Theriault et al., Atherosclerosis 2002;160:21-30 Effects of -Tocotrienol on VCAM-1, ICAM-1 and E-selectin expression in in cultured endothelial cells

21 A. Theriault et al., Atherosclerosis 2002;160:21-30 Effects of -tocotrienol and analogs on the adherence of monocytes to HUVEC

22 A. Theriault et al., Atherosclerosis 2002;160:21-30 Effect of farnesol and geranylgeraniol on the inhibitor effect of -tocotrienol on monocyte adherence to HUVEC

23 Asaf A. Qureshi et al., J Nutr 2001;131: Effect of -tocopherol, Tocotrienol-Rich Fraction (TRF 25 ), and didesmethyl tocotrienol (d-P 25 -T3) on total and LDL cholesterol in C57BL/6 apoE mice

24 Asaf A. Qureshi et al., J Nutr 2001;131: Effect of -tocopherol, Tocotrienol-Rich Fraction (TRF 25 ), and didesmethyl tocotrienol (d-P 25 -T3) on esperimental atherosclerotic plaque formation

25 A. Theriault et al., Clinical Biochemistry 1999;Vol 32: Mechanism by which tocotrienol inhibits the generation of foam cells

26 Randomised controlled trial of Tocopherol in pateints with coronary disease: Cambridge Heart Antioxidant Study (CHAOS) N.G. Stephens et al, Lancet, 1996; Vol 347,

27 Randomised controlled trial of Tocopherol in pateints with coronary disease: Cambridge Heart Antioxidant Study (CHAOS) N.G. Stephens et al, Lancet, 1996; Vol 347,

28 Randomised controlled trial of Tocopherol in pateints with coronary disease: Cambridge Heart Antioxidant Study (CHAOS) N.G. Stephens et al, Lancet, 1996; Vol 347,

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30 A. Theriault et al., Atherosclerosis 2002;160:21-30 Effects of -Tocotrienol and analogs on the expression of adhesion molecules in cultured endothelial cells -TS: -tocopheryl succinate -T: -tocopherol -T3: -tocotrienol

31 R. Ricciarelli et al., Circulation 2000;102: tocopherol reduces CD36 scavenger receptor expression in smooth muscle cells

32 S. Devaraj et al., J Lipid Res 2001;42: tocopherol reduces CD36 scavenger receptor expression in monocyte-derived macrophages AT: -tocopherol

33 S. Devaraj et al., J Lipid Res 2001;42: Effect of -tocopherol on AcLDL- and OxLDL- induced CD36 scavenger receptor expression

34 S. Devaraj et al., J Lipid Res 2001;42: Effect of -tocopherol on cholesteryl ester accumulation in macrophages

35 Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma intramurale maturo complicanze rottura cappa fibrosa placca fibrosa/ calcifica erosione endoteliale STENOSITROMBOSITROMBOSIRIMODELLAMENTO


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