Banca delle cornee e trapianto (cheratoplastica) endoteliale: presente e futuro
Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma...
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Transcript of Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma...
![Page 1: Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma intramurale maturo complicanze rottura cappa fibrosa.](https://reader035.fdocuments.net/reader035/viewer/2022062312/5542eb4f497959361e8bf16e/html5/thumbnails/1.jpg)
Processo infiammatorioProcesso infiammatorio
arteria arteria normalenormale
attivazione attivazione endotelialeendoteliale
progressioneprogressione
strie strie lipidichelipidiche
ateroma ateroma intramurale intramurale
maturomaturo
complicanzecomplicanze
rottura rottura cappa cappa fibrosafibrosa
placca placca fibrosa/ fibrosa/ calcificacalcifica
erosione erosione endotelialeendoteliale
STENOSISTENOSITROMBOSITROMBOSI TROMBOSITROMBOSIRIMODELLAMENTORIMODELLAMENTO
![Page 2: Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma intramurale maturo complicanze rottura cappa fibrosa.](https://reader035.fdocuments.net/reader035/viewer/2022062312/5542eb4f497959361e8bf16e/html5/thumbnails/2.jpg)
The mevalonate pathway
Acetyl-CoA
HMG-CoA
Mevalonate
Farnesyl-PP
Squalene
Cholesterol
Geranylgeranyl Transferase
Farnesyl Transferase
HMG-CoA Reductase Statins
Farnesylated proteins
Trans Trans Geranygeranyl-PP
Ubiquinones
Dolichols
Geranylgeranylatedprotein
The Mevalonate The Mevalonate PathwayPathwayAcetyl-CoA
HMG-CoA
Mevalonate
Isopentenyl-PP
Geranyl-PP
Farnesyl-PP
Prenylated Proteins
HMG-CoA Reductase Statins
Dolichols
2-cis Geranylgeranyl-PP
all-trans Geranylgeranyl-PP
Ubiquinone
Squalene
Cholesterol
X
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Rex A. Parker et al, The Journal of Biological Chemistry 1993;Nov. 6:11230-11238
-Tocotrienol decrease incorporation of acetate but not mevalonate into cholesterol in HepG2 cells
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Rex A. Parker et al, The Journal of Biological Chemistry 1993;Nov. 6:11230-11238
Suppression of HMG-CoA reductase total activity correlates with inhibition of cholesterol synthesis by -tocotrienol in HepG2 cells
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A. Theriault et al., Clinical Biochemistry 1999;Vol 32:309-319
Mechanism of the cholesterol suppressive action of tocotrienol
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A. Theriault et al., Clinical Biochemistry 1999;Vol 32:309-319
Mechanism for the reduction in low density lipoprotein (LDL) by tocotrienol
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Asaf A. Qureshi et al., Atherosclerosis 2002;161:199-207
Effects of of Tocotrienol-Rich Fraction (TRF25) on serum lipid parameters in hypercolesterolemic human subjects
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Asaf A. Qureshi et al., Journal of Nutritional Biochemistry 2001;12:318-329
Synergistic effect of of Tocotrienol-Rich Fraction (TRF25) and lovastatin
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Asaf A. Qureshi et al., Journal of Nutritional Biochemistry 2001;12:318-329
Serum lipid parameters in GROUP A
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Asaf A. Qureshi et al., Journal of Nutritional Biochemistry 2001;12:318-329
Serum lipid parameters in GROUP B
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Formazione della Placca AteroscleroticaFormazione della Placca AteroscleroticaAttivazione endoteliale
up-regulation molecole di adesione
migrazione leucocitaria
aumentata
permeabilità endoteliale
Shear stressintermittente
F.di R.LDL
Molecole di Adesione Selectine Immunoglobuline endoteliali
Chemoattrattanti Chemochine
Infiammazione
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formazione “strie
lipidiche”
migrazione cellule
muscolari lisce
ingrandimento nucleo lipidico
LDL
Fattori di Crescita Grow Factors
Formazione della Placca Formazione della Placca AteroscleroticaAterosclerotica
“ lesione intermedia”
Infiammazione
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FormazioneFormazione della Placca Ateroscleroticadella Placca Aterosclerotica
Enzimi litici – Fattori della CoagulazioneMetalloproteinasi
“ lesione avanzata”
Infiammazione
assottigliamento del
cappuccio fibroso
(erosione)rottura della
placca (shoulder region)
TROMBOSI
F.di R.LDL
Fattore Tissutale
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The mevalonate pathway
Acetyl-CoA
HMG-CoA
Mevalonate
Farnesyl-PP
Squalene
Cholesterol
Geranylgeranyl Transferase
Farnesyl Transferase
HMG-CoA Reductase Statins
Farnesylated proteins
Trans Trans Geranygeranyl-PP
Ubiquinones
Dolichols
Geranylgeranylatedprotein
The Mevalonate The Mevalonate PathwayPathwayAcetyl-CoA
HMG-CoA
Mevalonate
Isopentenyl-PP
Geranyl-PP
Farnesyl-PP
Prenylated Proteins
HMG-CoA Reductase Statins
Dolichols
2-cis Geranylgeranyl-PP
all-trans Geranylgeranyl-PP
Ubiquinone
Squalene
Cholesterol
X
![Page 15: Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma intramurale maturo complicanze rottura cappa fibrosa.](https://reader035.fdocuments.net/reader035/viewer/2022062312/5542eb4f497959361e8bf16e/html5/thumbnails/15.jpg)
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A. Theriault et al., Atherosclerosis 2002;160:21-30
Concentration dependent effects of -Tocotrienol on VCAM-1 expression in cultured endothelial cells
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A. Theriault et al., Atherosclerosis 2002;160:21-30
Effects of -Tocotrienol on VCAM-1, ICAM-1 and E-selectin expressionin in cultured endothelial cells
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A. Theriault et al., Atherosclerosis 2002;160:21-30
Effects of -tocotrienol and analogs on
the adherence of monocytes to HUVEC
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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
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Asaf A. Qureshi et al., J Nutr 2001;131:2606-2618
Effect of -tocopherol, Tocotrienol-Rich Fraction (TRF25), and didesmethyl tocotrienol (d-P25-T3) on total and LDL cholesterol in
C57BL/6 apoE mice
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Asaf A. Qureshi et al., J Nutr 2001;131:2606-2618
Effect of -tocopherol, Tocotrienol-Rich Fraction (TRF25), and didesmethyl tocotrienol (d-P25-T3) on esperimental atherosclerotic
plaque formation
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A. Theriault et al., Clinical Biochemistry 1999;Vol 32:309-319
Mechanism by which tocotrienol inhibits
the generation of foam cells
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Randomised controlled trial of Tocopherol in pateints with coronary disease: Cambridge Heart Antioxidant Study (CHAOS)
N.G. Stephens et al, Lancet, 1996; Vol 347, 781-86
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Randomised controlled trial of Tocopherol in pateints with coronary disease: Cambridge Heart Antioxidant Study (CHAOS)
N.G. Stephens et al, Lancet, 1996; Vol 347, 781-86
![Page 27: Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma intramurale maturo complicanze rottura cappa fibrosa.](https://reader035.fdocuments.net/reader035/viewer/2022062312/5542eb4f497959361e8bf16e/html5/thumbnails/27.jpg)
Randomised controlled trial of Tocopherol in pateints with coronary disease: Cambridge Heart Antioxidant Study (CHAOS)
N.G. Stephens et al, Lancet, 1996; Vol 347, 781-86
![Page 28: Processo infiammatorio arteria normale attivazione endoteliale progressione strie lipidiche ateroma intramurale maturo complicanze rottura cappa fibrosa.](https://reader035.fdocuments.net/reader035/viewer/2022062312/5542eb4f497959361e8bf16e/html5/thumbnails/28.jpg)
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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
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R. Ricciarelli et al., Circulation 2000;102:82-87
-tocopherol reduces CD36 scavenger receptor expression in smooth muscle cells
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S. Devaraj et al., J Lipid Res 2001;42:521-527
-tocopherol reduces CD36 scavenger receptor expression in monocyte-derived macrophages
AT: -tocopherol
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S. Devaraj et al., J Lipid Res 2001;42:521-527
Effect of -tocopherol on AcLDL- and OxLDL-induced CD36 scavenger receptor expression
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S. Devaraj et al., J Lipid Res 2001;42:521-527
Effect of -tocopherol on cholesteryl ester
accumulation in macrophages
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Processo infiammatorioProcesso infiammatorio
arteria arteria normalenormale
attivazione attivazione endotelialeendoteliale
progressioneprogressione
strie strie lipidichelipidiche
ateroma ateroma intramurale intramurale
maturomaturo
complicanzecomplicanze
rottura rottura cappa cappa fibrosafibrosa
placca placca fibrosa/ fibrosa/ calcificacalcifica
erosione erosione endotelialeendoteliale
STENOSISTENOSITROMBOSITROMBOSI TROMBOSITROMBOSIRIMODELLAMENTORIMODELLAMENTO