Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction
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 agi...
| Main Authors: | , , , , |
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| Format: | Journal Article |
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BioMed Central Ltd.
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/5769 |
| _version_ | 1848744889137758208 |
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| author | Takechi, Ryu Pallebage-Gamarallage, Menuka Lam, Virginie Giles, Corey Mamo, John |
| author_facet | Takechi, Ryu Pallebage-Gamarallage, Menuka Lam, Virginie Giles, Corey Mamo, John |
| author_sort | Takechi, Ryu |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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-ß (Aß). 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 Aß. 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. |
| first_indexed | 2025-11-14T06:08:38Z |
| format | Journal Article |
| id | curtin-20.500.11937-5769 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:08:38Z |
| publishDate | 2014 |
| publisher | BioMed Central Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-57692017-09-13T15:36:21Z Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction Takechi, Ryu Pallebage-Gamarallage, Menuka Lam, Virginie Giles, Corey Mamo, John Apolipoprotein B Probucol Brain capillaries Neuroinflammation Saturated fatty acids Amyloid-ß Blood–brain barrier Enterocytes 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-ß (Aß). 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 Aß. 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/5769 10.1186/1476-511X-13-91 BioMed Central Ltd. fulltext |
| spellingShingle | Apolipoprotein B Probucol Brain capillaries Neuroinflammation Saturated fatty acids Amyloid-ß Blood–brain barrier Enterocytes Takechi, Ryu Pallebage-Gamarallage, Menuka Lam, Virginie Giles, Corey Mamo, John Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction |
| title | Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction |
| title_full | Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction |
| title_fullStr | Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction |
| title_full_unstemmed | Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction |
| title_short | Long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction |
| title_sort | long-term probucol therapy continues to suppress markers of neurovascular inflammation in a dietary induced model of cerebral capillary dysfunction |
| topic | Apolipoprotein B Probucol Brain capillaries Neuroinflammation Saturated fatty acids Amyloid-ß Blood–brain barrier Enterocytes |
| url | http://hdl.handle.net/20.500.11937/5769 |