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Roles of lipoproteins

Roles of lipoproteins. transport of triglycerides from intestine & liver to peripheral tissues (dietary & stored fatty acids) transport of cholesterol & phospholipids to peripheral tissues, glands, and liver (« reverse ») transport of liposoluble vitamins

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Roles of lipoproteins

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  1. Roles of lipoproteins • transport of triglycerides from intestine & liver to peripheral tissues (dietary & stored fatty acids) • transport of cholesterol & phospholipids to peripheral tissues, glands, and liver (« reverse ») • transport of liposoluble vitamins • transport of antioxidant enzymes • neutralization of endotoxins • effect of oxidised lipids on immune defenses, inflammation, and thrombosis passage of some particles from circulation to intimal space of arterial vessels (in both directions)

  2. Structure of apolipoprotein B JP Segrest et al, J. Lipid Res., 2001

  3. NORMAL REC. DEFICIENT LDL LDL IDL IDL VLDL VLDL FA FA

  4. Sous-types de LDL LDL normales LDL rec • sd LDL • Passage intima fragilité • cytotoxicité • LDL modifiées rétention intimale • cytotoxicité

  5. Les lipoprotéines dans la paroi artérielle Nordestgaard BG and Nielsen LB, Curr. Opin. Lipidol., 1994

  6. Cholesterol transport by HDL (normal) LpB receptors Other lipoproteins Peripheral Tissues CETP HDL Cholesterol ABC syst LCAT SR-B1/CLA Apo AI Blood Apo AI HDL Apo AI Cholesterol & bile acids Apo AI ABC syst SR-B1/CLA Arterial wall Cholesterol Steroidogenic tissues Steroid hormones

  7. Roles of HDL: normal conditions • Reverse cholesterol transport from periphery (including macrophages, endothelial cells, SMC, etc…) to liver • Cholesterol transport to steroidogenic glands • Transport of other lipid components & vitamins • Protection of LDL against peroxidative damage • Stabilization of prostacyclin • Major carrier of LPS-binding protein (LBP)

  8. LIPIDES ET LIPOPROTEINES PLASMATIQUES Les Gènes sont lesbriques et le mortier du corps, et le Comportement en est l’architecte RJ Deckelbaum

  9. La Lésion Athéromateuse • Maladie inflammatoire chronique de la paroi vasculaire • Apparition récente dans évolution humaine • Liée au mode de vie (nutrition, tabac, activité physique, ..) • Liée au patrimoine génétique (familles, ethnies, …) • Liée à autres pathologies (lipides, diabète, hypertension, inflammations, …) et traitements (stéroïdes, anti-rejets, ...) • Distribution géographique (mode de vie occidental, centres urbains, …) Largement réversible  prévention efficace

  10. La paroi artérielle normale Cellules endotheliales CML contractiles

  11. Début athérosclérose – Formation de la strie graisseuse Les monocytes migrent dans l’intima, se differencient en macrophages, se gorgent de lipides, et forment cell. spumeuses Lipid Des lymphocytes-T accompagnent les monocytes dans l’intima

  12. La couche fibreuse et la plaque athéromateuse Les CML qui ont migré changent de phénotype (de ‘contractile’ à ‘cicatrisation’), et produisent les composants de la couche fibreuse Noyau lipidique Adventice Weissberg, 1999

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