Transendothelial transport of lipoproteins

The accumulation of low-density lipoproteins (LDL) in the arterial wall plays a pivotal role in the initiation and pathogenesis of atherosclerosis. Conversely, the removal of cholesterol from the intima by cholesterol efflux to high density lipoproteins (HDL) and subsequent reverse cholesterol trans...

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Bibliographic Details
Published in:Atherosclerosis 2020-12, Vol.315, p.111-125
Main Authors: Jang, Erika, Robert, Jerome, Rohrer, Lucia, von Eckardstein, Arnold, Lee, Warren L.
Format: Article
Language:English
Subjects:
ALK-1
Caveolin
HDL
LDL
SR-BI
Transcytosis
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Summary:The accumulation of low-density lipoproteins (LDL) in the arterial wall plays a pivotal role in the initiation and pathogenesis of atherosclerosis. Conversely, the removal of cholesterol from the intima by cholesterol efflux to high density lipoproteins (HDL) and subsequent reverse cholesterol transport shall confer protection against atherosclerosis. To reach the subendothelial space, both LDL and HDL must cross the intact endothelium. Traditionally, this transit is explained by passive filtration. This dogma has been challenged by the identification of several rate-limiting factors namely scavenger receptor SR-BI, activin like kinase 1, and caveolin-1 for LDL as well as SR-BI, ATP binding cassette transporter G1, and endothelial lipase for HDL. In addition, estradiol, vascular endothelial growth factor, interleukins 6 and 17, purinergic signals, and sphingosine-1-phosphate were found to regulate transendothelial transport of either LDL or HDL. Thorough understanding of transendothelial lipoprotein transport is expected to elucidate new therapeutic targets for the treatment or prevention of atherosclerotic cardiovascular disease and the development of strategies for the local delivery of drugs or diagnostic tracers into diseased tissues including atherosclerotic lesions. [Display omitted] •The endothelium limits the entry and exit of lipoproteins into and from the arterial wall, respectively.•SR-BI, activin like kinase 1, and caveolin-1 as well as GPER and sphingosine-1-phosphate regulate the transcytosis of LDL.•SR-BI, ABCG1, endothelial lipase, the ecto-ATPase/P2Y-receptor axis, VEGF, IL-6/17, and S1P regulate HDL transcytosis.
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2020.09.020