Tags

Type your tag names separated by a space and hit enter

Post-prandial lipid metabolism, lipid-modulating agents and cerebrovascular integrity: implications for dementia risk.

Abstract

Amyloid-β (Aβ) is secreted as an apolipoprotein of nascent triglyceride-rich lipoproteins (TRL) derived from both liver and intestine, but is better recognized as the principal protein component of senile plaque in subjects with Alzheimer's disease. Recent studies suggest that exaggerated exposure to plasma Aβ can compromise cerebrovascular integrity, resulting thereafter in blood to brain delivery of plasma proteins including TRL-Aβ. Parenchymal deposits of Aβ show significant immunoreactivity to apolipoprotein B (apo B), consistent with the notion of lipoprotein-Aβ entrapment. In wild type mice chronically fed physiologically relevant diets, saturated fats (SFA) enhance chylomicron-Aβ concomitant with disturbances in blood-brain barrier integrity. Similarly, dietary cholesterol promotes cerebrovascular extravasation of apo B lipoprotein-Aβ. In this study, we investigated the effects of atorvastatin, pravastatin and probucol on dietary-fat induced disturbances in BBB function. Atorvastatin, a lipid soluble HMG-CoA reductase inhibitor prevented SFA induced parenchymal extravasation of apo B-Aβ at 28 days when incorporated into the diet at 20 mg/kg. In contrast, pravastatin a water soluble agent had no effect on BBB integrity at an equivalent dose. In cholesterol supplemented mice, probucol maintained BBB function and extravasation of apo B-Aβ was not evident. The findings suggest that some lipid-modulating agents may be effective in ameliorating the negative effects of saturated fats and cholesterol on cerebrovascular integrity.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Faculty of Health Sciences, Curtin University of Technology and ATN Centre for Metabolic Health and Fitness, Perth, WA, Australia.

    , , , ,

    Source

    Atherosclerosis. Supplements 11:1 2010 Jun pg 49-54

    MeSH

    Amyloid beta-Peptides
    Animals
    Anticholesteremic Agents
    Apolipoproteins B
    Blood-Brain Barrier
    Cerebrovascular Disorders
    Cholesterol, Dietary
    Chylomicrons
    Dementia
    Humans
    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Hypolipidemic Agents
    Lipid Metabolism
    Mice
    Postprandial Period
    Risk Factors

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    20430703

    Citation

    Pallebage-Gamarallage, Menuka M S., et al. "Post-prandial Lipid Metabolism, Lipid-modulating Agents and Cerebrovascular Integrity: Implications for Dementia Risk." Atherosclerosis. Supplements, vol. 11, no. 1, 2010, pp. 49-54.
    Pallebage-Gamarallage MM, Takechi R, Lam V, et al. Post-prandial lipid metabolism, lipid-modulating agents and cerebrovascular integrity: implications for dementia risk. Atheroscler Suppl. 2010;11(1):49-54.
    Pallebage-Gamarallage, M. M., Takechi, R., Lam, V., Galloway, S., Dhaliwal, S., & Mamo, J. C. (2010). Post-prandial lipid metabolism, lipid-modulating agents and cerebrovascular integrity: implications for dementia risk. Atherosclerosis. Supplements, 11(1), pp. 49-54. doi:10.1016/j.atherosclerosissup.2010.04.002.
    Pallebage-Gamarallage MM, et al. Post-prandial Lipid Metabolism, Lipid-modulating Agents and Cerebrovascular Integrity: Implications for Dementia Risk. Atheroscler Suppl. 2010;11(1):49-54. PubMed PMID: 20430703.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Post-prandial lipid metabolism, lipid-modulating agents and cerebrovascular integrity: implications for dementia risk. AU - Pallebage-Gamarallage,Menuka M S, AU - Takechi,Ryusuke, AU - Lam,Virginie, AU - Galloway,Susan, AU - Dhaliwal,Satvinder, AU - Mamo,John C L, Y1 - 2010/04/28/ PY - 2010/03/18/received PY - 2010/04/08/revised PY - 2010/04/08/accepted PY - 2010/5/1/entrez PY - 2010/5/1/pubmed PY - 2011/6/1/medline SP - 49 EP - 54 JF - Atherosclerosis. Supplements JO - Atheroscler Suppl VL - 11 IS - 1 N2 - Amyloid-β (Aβ) is secreted as an apolipoprotein of nascent triglyceride-rich lipoproteins (TRL) derived from both liver and intestine, but is better recognized as the principal protein component of senile plaque in subjects with Alzheimer's disease. Recent studies suggest that exaggerated exposure to plasma Aβ can compromise cerebrovascular integrity, resulting thereafter in blood to brain delivery of plasma proteins including TRL-Aβ. Parenchymal deposits of Aβ show significant immunoreactivity to apolipoprotein B (apo B), consistent with the notion of lipoprotein-Aβ entrapment. In wild type mice chronically fed physiologically relevant diets, saturated fats (SFA) enhance chylomicron-Aβ concomitant with disturbances in blood-brain barrier integrity. Similarly, dietary cholesterol promotes cerebrovascular extravasation of apo B lipoprotein-Aβ. In this study, we investigated the effects of atorvastatin, pravastatin and probucol on dietary-fat induced disturbances in BBB function. Atorvastatin, a lipid soluble HMG-CoA reductase inhibitor prevented SFA induced parenchymal extravasation of apo B-Aβ at 28 days when incorporated into the diet at 20 mg/kg. In contrast, pravastatin a water soluble agent had no effect on BBB integrity at an equivalent dose. In cholesterol supplemented mice, probucol maintained BBB function and extravasation of apo B-Aβ was not evident. The findings suggest that some lipid-modulating agents may be effective in ameliorating the negative effects of saturated fats and cholesterol on cerebrovascular integrity. SN - 1878-5050 UR - https://www.unboundmedicine.com/medline/citation/20430703/Post_prandial_lipid_metabolism_lipid_modulating_agents_and_cerebrovascular_integrity:_implications_for_dementia_risk_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5688(10)70227-0 DB - PRIME DP - Unbound Medicine ER -