Transendothelial transport of lipoproteins.

Erika Jang, Jerome Robert, Lucia Rohrer, Arnold von Eckardstein, Warren L Lee

Journal: Atherosclerosis 2021;315():111-125

PMID: 33032832

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Keenan Centre for Biomedical Research, St. Michael's Hospital, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada.; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Switzerland.; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Switzerland. Electronic address: [email protected].; Keenan Centre for Biomedical Research, St. Michael's Hospital, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada; Interdepartmental Division of Critical Care, Department of Medicine, University of Toronto, Canada; Department of Biochemistry, University of Toronto, Canada; Institute of Medical Science, University of Toronto, Canada. Electronic address: [email protected].

DOI: 10.1016/j.atherosclerosis.2020.09.020

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MeSH Terms: Lipoproteins, Lipoproteins, HDL, Lipoproteins, LDL, Scavenger Receptors, Class B, Vascular Endothelial Growth Factor A