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

Research

Virginie Lam¹  John CL Mamo¹  Ryusuke Takechi¹  Menuka M Pallebage-Gamarallage¹  Corey Giles¹ 

[1] School of Public Health, and CHIRI Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Bentley, GPO Box U1987, 6845, Perth, WA, Australia;

关键词: Brain capillaries;    Amyloid-β;    Apolipoprotein B;    Blood–brain barrier;    Enterocytes;    Neuroinflammation;    Probucol;    Saturated fatty acids;   

DOI  :  10.1186/1476-511X-13-91

 received in 2014-05-07, accepted in 2014-05-28,  发布年份 2014

来源: Springer

【 摘 要 】

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

【 授权许可】

Unknown   
© Takechi et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.