Tags

Type your tag names separated by a space and hit enter

Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction.

Abstract

BACKGROUND

Probucol has been shown to prevent cerebral capillary disturbances characterized by blood-to-brain extravasation of plasma derived proteins and neurovascular inflammation in mice maintained on western-styled diets for 12 weeks. However the effect of probucol on capillary integrity in aging models with capillary dysfunction is not known.

METHODS

Wild-type C57BL6 mice were randomized to a low-fat (LF); saturated-fat (SFA); or SFA + Probucol diet for up to12 months of intervention.

RESULTS

Mice fed the LF diet had substantially greater parenchymal abundance of plasma derived IgG and apo B lipoproteins at 12 months, compared to LF mice at 3 months of intervention. Markers of neurovascular inflammation were also greater at 12 months in LF fed mice compared to LF mice at 3 months. The SFA diet exacerbated the aging induced parenchymal abundance of IgG and of apo B lipoproteins and neurovascular inflammation at 12 months. The SFA effects were associated with increased production of intestinal lipoprotein amyloid-β (Aβ). The co-provision of probucol with the SFA completely abolished heightened inflammation at 12 months. Probucol attenuated SFA-induced capillary permeability but had only a modest inhibitory effect on parenchymal retention of apoB lipoproteins. The improvements in markers of inflammation and capillary integrity because of probucol correlated with enterocytic genesis of chylomicron Aβ.

CONCLUSION

In this long-term feeding study, probucol profoundly suppressed dietary SFA induced disturbances in capillary integrity but had a more modest effect on age-associated changes.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    , , , ,

    School of Public Health, and CHIRI Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Bentley, GPO Box U1987, Perth 6845, WA, Australia. J.Mamo@curtin.edu.au.

    Source

    Lipids in health and disease 13: 2014 Jun 03 pg 91

    MeSH

    Animals
    Apolipoproteins B
    Blood-Brain Barrier
    Capillaries
    Diet, Fat-Restricted
    Female
    Immunoglobulin G
    Inflammation
    Mice
    Mice, Inbred C57BL
    Probucol

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24890126

    Citation

    Takechi, Ryusuke, et al. "Long-term Probucol Therapy Continues to Suppress Markers of Neurovascular Inflammation in a Dietary Induced Model of Cerebral Capillary Dysfunction." Lipids in Health and Disease, vol. 13, 2014, p. 91.
    Takechi R, Pallebage-Gamarallage MM, Lam V, et al. Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction. Lipids Health Dis. 2014;13:91.
    Takechi, R., Pallebage-Gamarallage, M. M., Lam, V., Giles, C., & Mamo, J. C. (2014). Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction. Lipids in Health and Disease, 13, p. 91. doi:10.1186/1476-511X-13-91.
    Takechi R, et al. Long-term Probucol Therapy Continues to Suppress Markers of Neurovascular Inflammation in a Dietary Induced Model of Cerebral Capillary Dysfunction. Lipids Health Dis. 2014 Jun 3;13:91. PubMed PMID: 24890126.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction. AU - Takechi,Ryusuke, AU - Pallebage-Gamarallage,Menuka M, AU - Lam,Virginie, AU - Giles,Corey, AU - Mamo,John Cl, Y1 - 2014/06/03/ PY - 2014/05/07/received PY - 2014/05/28/accepted PY - 2014/6/4/entrez PY - 2014/6/4/pubmed PY - 2014/12/15/medline SP - 91 EP - 91 JF - Lipids in health and disease JO - Lipids Health Dis VL - 13 N2 - BACKGROUND: Probucol has been shown to prevent cerebral capillary disturbances characterized by blood-to-brain extravasation of plasma derived proteins and neurovascular inflammation in mice maintained on western-styled diets for 12 weeks. However the effect of probucol on capillary integrity in aging models with capillary dysfunction is not known. METHODS: Wild-type C57BL6 mice were randomized to a low-fat (LF); saturated-fat (SFA); or SFA + Probucol diet for up to12 months of intervention. RESULTS: Mice fed the LF diet had substantially greater parenchymal abundance of plasma derived IgG and apo B lipoproteins at 12 months, compared to LF mice at 3 months of intervention. Markers of neurovascular inflammation were also greater at 12 months in LF fed mice compared to LF mice at 3 months. The SFA diet exacerbated the aging induced parenchymal abundance of IgG and of apo B lipoproteins and neurovascular inflammation at 12 months. The SFA effects were associated with increased production of intestinal lipoprotein amyloid-β (Aβ). The co-provision of probucol with the SFA completely abolished heightened inflammation at 12 months. Probucol attenuated SFA-induced capillary permeability but had only a modest inhibitory effect on parenchymal retention of apoB lipoproteins. The improvements in markers of inflammation and capillary integrity because of probucol correlated with enterocytic genesis of chylomicron Aβ. CONCLUSION: In this long-term feeding study, probucol profoundly suppressed dietary SFA induced disturbances in capillary integrity but had a more modest effect on age-associated changes. SN - 1476-511X UR - https://www.unboundmedicine.com/medline/citation/24890126/Long_term_probucol_therapy_continues_to_suppress_markers_of_neurovascular_inflammation_in_a_dietary_induced_model_of_cerebral_capillary_dysfunction_ L2 - https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-13-91 DB - PRIME DP - Unbound Medicine ER -