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26-06-2023 | Arterial Occlusive Disease

LDL Transcytosis by the Arterial Endothelium—Atherosclerosis by a Thousand Cuts?

Authors: Tse Wing Winnie Ho, Andria Henry, Warren L. Lee

Published in: Current Atherosclerosis Reports | Issue 8/2023

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Abstract

Purpose of Review

The accumulation of LDL in the arterial intima is an initiating event in atherosclerosis. After decades of controversy, it is now clear that transcytosis of LDL across an intact endothelial monolayer contributes to its intimal deposition. We review recent observations in this field and address the question of whether LDL transcytosis can be manipulated therapeutically.

Recent Findings

The development of a live-cell imaging method for studying transcytosis using total internal reflection fluorescence (TIRF) microscopy has catalyzed recent discoveries. LDL transcytosis is mediated by SR-BI and ALK1. Estrogen down-regulates SR-BI and inhibits LDL transcytosis, while the nuclear structural protein HMGB1 promotes LDL transcytosis. LDL transcytosis by ALK1 is independent of the receptor’s kinase activity and is antagonized by BMP9, ALK1’s canonical ligand. Inflammation stimulates LDL transcytosis.

Summary

Identifying the function and mechanisms of LDL transcytosis may ultimately permit its therapeutic manipulation.
Literature
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Metadata
Title
LDL Transcytosis by the Arterial Endothelium—Atherosclerosis by a Thousand Cuts?
Authors
Tse Wing Winnie Ho
Andria Henry
Warren L. Lee
Publication date
26-06-2023
Publisher
Springer US
Published in
Current Atherosclerosis Reports / Issue 8/2023
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-023-01118-x

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