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HDL as Bidirectional Lipid Vectors: Time for New Paradigms

The anti-atherogenic properties of high-density lipoproteins (HDL) have been explained mainly by reverse cholesterol transport (RCT) from peripheral tissues to the liver. The RCT seems to agree with most of the negative epidemiological correlations between HDL cholesterol levels and coronary artery...

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Autores principales: Luna-Luna, María, Niesor, Eric, Pérez-Méndez, Óscar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138557/
https://www.ncbi.nlm.nih.gov/pubmed/35625916
http://dx.doi.org/10.3390/biomedicines10051180
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author Luna-Luna, María
Niesor, Eric
Pérez-Méndez, Óscar
author_facet Luna-Luna, María
Niesor, Eric
Pérez-Méndez, Óscar
author_sort Luna-Luna, María
collection PubMed
description The anti-atherogenic properties of high-density lipoproteins (HDL) have been explained mainly by reverse cholesterol transport (RCT) from peripheral tissues to the liver. The RCT seems to agree with most of the negative epidemiological correlations between HDL cholesterol levels and coronary artery disease. However, therapies designed to increase HDL cholesterol failed to reduce cardiovascular risk, despite their capacity to improve cholesterol efflux, the first stage of RCT. Therefore, the cardioprotective role of HDL may not be explained by RCT, and it is time for new paradigms about the physiological function of these lipoproteins. It should be considered that the main HDL apolipoprotein, apo AI, has been highly conserved throughout evolution. Consequently, these lipoproteins play an essential physiological role beyond their capacity to protect against atherosclerosis. We propose HDL as bidirectional lipid vectors carrying lipids from and to tissues according to their local context. Lipid influx mediated by HDL appears to be particularly important for tissue repair right on site where the damage occurs, including arteries during the first stages of atherosclerosis. In contrast, the HDL-lipid efflux is relevant for secretory cells where the fusion of intracellular vesicles drastically enlarges the cytoplasmic membrane with the potential consequence of impairment of cell function. In such circumstances, HDL could deliver some functional lipids and pick up not only cholesterol but an integral part of the membrane in excess, restoring the viability of the secretory cells. This hypothesis is congruent with the beneficial effects of HDL against atherosclerosis as well as with their capacity to induce insulin secretion and merits experimental exploration.
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spelling pubmed-91385572022-05-28 HDL as Bidirectional Lipid Vectors: Time for New Paradigms Luna-Luna, María Niesor, Eric Pérez-Méndez, Óscar Biomedicines Review The anti-atherogenic properties of high-density lipoproteins (HDL) have been explained mainly by reverse cholesterol transport (RCT) from peripheral tissues to the liver. The RCT seems to agree with most of the negative epidemiological correlations between HDL cholesterol levels and coronary artery disease. However, therapies designed to increase HDL cholesterol failed to reduce cardiovascular risk, despite their capacity to improve cholesterol efflux, the first stage of RCT. Therefore, the cardioprotective role of HDL may not be explained by RCT, and it is time for new paradigms about the physiological function of these lipoproteins. It should be considered that the main HDL apolipoprotein, apo AI, has been highly conserved throughout evolution. Consequently, these lipoproteins play an essential physiological role beyond their capacity to protect against atherosclerosis. We propose HDL as bidirectional lipid vectors carrying lipids from and to tissues according to their local context. Lipid influx mediated by HDL appears to be particularly important for tissue repair right on site where the damage occurs, including arteries during the first stages of atherosclerosis. In contrast, the HDL-lipid efflux is relevant for secretory cells where the fusion of intracellular vesicles drastically enlarges the cytoplasmic membrane with the potential consequence of impairment of cell function. In such circumstances, HDL could deliver some functional lipids and pick up not only cholesterol but an integral part of the membrane in excess, restoring the viability of the secretory cells. This hypothesis is congruent with the beneficial effects of HDL against atherosclerosis as well as with their capacity to induce insulin secretion and merits experimental exploration. MDPI 2022-05-20 /pmc/articles/PMC9138557/ /pubmed/35625916 http://dx.doi.org/10.3390/biomedicines10051180 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Luna-Luna, María
Niesor, Eric
Pérez-Méndez, Óscar
HDL as Bidirectional Lipid Vectors: Time for New Paradigms
title HDL as Bidirectional Lipid Vectors: Time for New Paradigms
title_full HDL as Bidirectional Lipid Vectors: Time for New Paradigms
title_fullStr HDL as Bidirectional Lipid Vectors: Time for New Paradigms
title_full_unstemmed HDL as Bidirectional Lipid Vectors: Time for New Paradigms
title_short HDL as Bidirectional Lipid Vectors: Time for New Paradigms
title_sort hdl as bidirectional lipid vectors: time for new paradigms
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138557/
https://www.ncbi.nlm.nih.gov/pubmed/35625916
http://dx.doi.org/10.3390/biomedicines10051180
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