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Open AccessArticle

Vasoprotective Functions of High-Density Lipoproteins Relevant to Alzheimer’s Disease Are Partially Conserved in Apolipoprotein B-Depleted Plasma

1
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
2
Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
*
Author to whom correspondence should be addressed.
Co-senior authors.
Int. J. Mol. Sci. 2019, 20(3), 462; https://doi.org/10.3390/ijms20030462
Received: 7 January 2019 / Revised: 19 January 2019 / Accepted: 21 January 2019 / Published: 22 January 2019
High-density lipoproteins (HDL) are known to have vasoprotective functions in peripheral arteries and many of these functions extend to brain-derived endothelial cells. Importantly, several novel brain-relevant HDL functions have been discovered using brain endothelial cells and in 3D bioengineered human arteries. The cerebrovascular benefits of HDL in healthy humans may partly explain epidemiological evidence suggesting a protective association of circulating HDL levels against Alzheimer’s Disease (AD) risk. As several methods exist to prepare HDL from plasma, here we compared cerebrovascular functions relevant to AD using HDL isolated by density gradient ultracentrifugation relative to apoB-depleted plasma prepared by polyethylene-glycol precipitation, a common high-throughput method to evaluate HDL cholesterol efflux capacity in clinical biospecimens. We found that apoB-depleted plasma was functionally equivalent to HDL isolated by ultracentrifugation in terms of its ability to reduce vascular Aβ accumulation, suppress TNFα-induced vascular inflammation and delay Aβ fibrillization. However, only HDL isolated by ultracentrifugation was able to suppress Aβ-induced vascular inflammation, improve Aβ clearance, and induce endothelial nitric oxide production. View Full-Text
Keywords: high-density lipoprotein (HDL); cerebrovasculature; endothelial cell; amyloid beta (Aβ); Alzheimer’s disease; blood-brain barrier (BBB); inflammation; cerebral amyloid angiopathy (CAA) high-density lipoprotein (HDL); cerebrovasculature; endothelial cell; amyloid beta (Aβ); Alzheimer’s disease; blood-brain barrier (BBB); inflammation; cerebral amyloid angiopathy (CAA)
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MDPI and ACS Style

Button, E.B.; Gilmour, M.; Cheema, H.K.; Martin, E.M.; Agbay, A.; Robert, J.; Wellington, C.L. Vasoprotective Functions of High-Density Lipoproteins Relevant to Alzheimer’s Disease Are Partially Conserved in Apolipoprotein B-Depleted Plasma. Int. J. Mol. Sci. 2019, 20, 462.

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