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Endocytosis of lipoproteins


Zanoni, Paolo; Velagapudi, Srividya; Yalcinkaya, Mustafa; Rohrer, Lucia; von Eckardstein, Arnold (2018). Endocytosis of lipoproteins. Atherosclerosis, 275:273-295.

Abstract

During their metabolism, all lipoproteins undergo endocytosis, either to be degraded intracellularly, for example in hepatocytes or macrophages, or to be re-secreted, for example in the course of transcytosis by endothelial cells. Moreover, there are several examples of internalized lipoproteins sequestered intracellularly, possibly to exert intracellular functions, for example the cytolysis of trypanosoma. Endocytosis and the subsequent intracellular itinerary of lipoproteins hence are key areas for understanding the regulation of plasma lipid levels as well as the biological functions of lipoproteins. Indeed, the identification of the low-density lipoprotein (LDL)-receptor and the unraveling of its transcriptional regulation led to the elucidation of familial hypercholesterolemia as well as to the development of statins, the most successful therapeutics for lowering of cholesterol levels and risk of atherosclerotic cardiovascular diseases. Novel limiting factors of intracellular trafficking of LDL and the LDL receptor continue to be discovered and to provide drug targets such as PCSK9. Surprisingly, the receptors mediating endocytosis of high-density lipoproteins or lipoprotein(a) are still a matter of controversy or even new discovery. Finally, the receptors and mechanisms, which mediate the uptake of lipoproteins into non-degrading intracellular itineraries for re-secretion (transcytosis, retroendocytosis), storage, or execution of intracellular functions, are largely unknown.

Abstract

During their metabolism, all lipoproteins undergo endocytosis, either to be degraded intracellularly, for example in hepatocytes or macrophages, or to be re-secreted, for example in the course of transcytosis by endothelial cells. Moreover, there are several examples of internalized lipoproteins sequestered intracellularly, possibly to exert intracellular functions, for example the cytolysis of trypanosoma. Endocytosis and the subsequent intracellular itinerary of lipoproteins hence are key areas for understanding the regulation of plasma lipid levels as well as the biological functions of lipoproteins. Indeed, the identification of the low-density lipoprotein (LDL)-receptor and the unraveling of its transcriptional regulation led to the elucidation of familial hypercholesterolemia as well as to the development of statins, the most successful therapeutics for lowering of cholesterol levels and risk of atherosclerotic cardiovascular diseases. Novel limiting factors of intracellular trafficking of LDL and the LDL receptor continue to be discovered and to provide drug targets such as PCSK9. Surprisingly, the receptors mediating endocytosis of high-density lipoproteins or lipoprotein(a) are still a matter of controversy or even new discovery. Finally, the receptors and mechanisms, which mediate the uptake of lipoproteins into non-degrading intracellular itineraries for re-secretion (transcytosis, retroendocytosis), storage, or execution of intracellular functions, are largely unknown.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
Dewey Decimal Classification:610 Medicine & health
540 Chemistry
Scopus Subject Areas:Health Sciences > Cardiology and Cardiovascular Medicine
Language:English
Date:August 2018
Deposited On:28 Feb 2019 12:24
Last Modified:29 Jul 2020 09:49
Publisher:Elsevier
ISSN:0021-9150
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.atherosclerosis.2018.06.881
PubMed ID:29980055

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