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

被引:9
|
作者
Button, Emily B. [1 ,2 ]
Gilmour, Megan [1 ,2 ]
Cheema, Harleen K. [1 ,2 ]
Martin, Emma M. [1 ,2 ]
Agbay, Andrew [1 ,2 ]
Robert, Jerome [1 ,2 ]
Wellington, Cheryl L. [1 ,2 ]
机构
[1] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 1Z3, Canada
[2] Univ British Columbia, Dept Pathol & Lab Med, Djavad Mowafaghian Ctr Brain Hlth, Vancouver, BC V6T 1Z3, Canada
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 03期
基金
加拿大健康研究院;
关键词
high-density lipoprotein (HDL); cerebrovasculature; endothelial cell; amyloid beta (A); Alzheimer's disease; blood-brain barrier (BBB); inflammation; cerebral amyloid angiopathy (CAA); CHOLESTEROL EFFLUX CAPACITY; CEREBRAL AMYLOID ANGIOPATHY; COGNITIVE FUNCTION; HDL CHOLESTEROL; DYSFUNCTIONAL HDL; MOUSE MODEL; LATE-LIFE; PATHWAYS;
D O I
10.3390/ijms20030462
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 A accumulation, suppress TNF-induced vascular inflammation and delay A fibrillization. However, only HDL isolated by ultracentrifugation was able to suppress A-induced vascular inflammation, improve A clearance, and induce endothelial nitric oxide production.
引用
收藏
页数:15
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