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HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm
BACKGROUND: The etiopathogenesis of abdominal aortic aneurysm (AAA) is still unclarified, but vascular inflammation and matrix metalloproteases activation have a recognized role in AAA development and progression. Circulating lipoproteins are involved in tissue inflammation and repair, particularly...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510680/ https://www.ncbi.nlm.nih.gov/pubmed/36172376 http://dx.doi.org/10.3389/fimmu.2022.935241 |
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author | Adorni, Maria Pia Palumbo, Marcella Marchi, Cinzia Zimetti, Francesca Ossoli, Alice Turri, Marta Bernini, Franco Hollan, Ivana Moláček, Jiří Treska, Vladislav Ronda, Nicoletta |
author_facet | Adorni, Maria Pia Palumbo, Marcella Marchi, Cinzia Zimetti, Francesca Ossoli, Alice Turri, Marta Bernini, Franco Hollan, Ivana Moláček, Jiří Treska, Vladislav Ronda, Nicoletta |
author_sort | Adorni, Maria Pia |
collection | PubMed |
description | BACKGROUND: The etiopathogenesis of abdominal aortic aneurysm (AAA) is still unclarified, but vascular inflammation and matrix metalloproteases activation have a recognized role in AAA development and progression. Circulating lipoproteins are involved in tissue inflammation and repair, particularly through the regulation of intracellular cholesterol, whose excess is associated to cell damage and proinflammatory activation. We analyzed lipoprotein metabolism and function in AAA and in control vasculopathic patients, to highlight possible non-atherosclerosis-related, specific abnormalities. METHODS: We measured fluorometrically serum esterified/total cholesterol ratio, as an index of lecithin-cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) activity in patients referred to vascular surgery either for AAA (n=30) or stenotic aortic/peripheral atherosclerosis (n=21) having similar burden of cardiovascular risk factors and disease. We measured high-density lipoprotein (HDL)-cholesterol efflux capacity (CEC), through the ATP-binding cassette G1 (ABCG1) and A1 (ABCA1) pathways and serum cell cholesterol loading capacity (CLC), by radioisotopic and fluorimetric methods, respectively. RESULTS: We found higher LCAT (+23%; p < 0.0001) and CETP (+49%; p < 0.0001) activity in AAA sera. HDL ABCG1-CEC was lower (−16%; p < 0.001) and ABCA1-CEC was higher (+31.7%; p < 0.0001) in AAA. Stratification suggests that smoking may partly contribute to these modifications. CEC and CETP activity correlated with CLC only in AAA. CONCLUSIONS: We demonstrated that compared to patients with stenotic atherosclerosis, patients with AAA had altered HDL metabolism and functions involved in their anti-inflammatory and tissue repair activity, particularly through the ABCG1-related intracellular signaling. Clarifying the relevance of this mechanism for AAA evolution might help in developing new diagnostic parameters and therapeutic targets for the early management of this condition. |
format | Online Article Text |
id | pubmed-9510680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95106802022-09-27 HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm Adorni, Maria Pia Palumbo, Marcella Marchi, Cinzia Zimetti, Francesca Ossoli, Alice Turri, Marta Bernini, Franco Hollan, Ivana Moláček, Jiří Treska, Vladislav Ronda, Nicoletta Front Immunol Immunology BACKGROUND: The etiopathogenesis of abdominal aortic aneurysm (AAA) is still unclarified, but vascular inflammation and matrix metalloproteases activation have a recognized role in AAA development and progression. Circulating lipoproteins are involved in tissue inflammation and repair, particularly through the regulation of intracellular cholesterol, whose excess is associated to cell damage and proinflammatory activation. We analyzed lipoprotein metabolism and function in AAA and in control vasculopathic patients, to highlight possible non-atherosclerosis-related, specific abnormalities. METHODS: We measured fluorometrically serum esterified/total cholesterol ratio, as an index of lecithin-cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) activity in patients referred to vascular surgery either for AAA (n=30) or stenotic aortic/peripheral atherosclerosis (n=21) having similar burden of cardiovascular risk factors and disease. We measured high-density lipoprotein (HDL)-cholesterol efflux capacity (CEC), through the ATP-binding cassette G1 (ABCG1) and A1 (ABCA1) pathways and serum cell cholesterol loading capacity (CLC), by radioisotopic and fluorimetric methods, respectively. RESULTS: We found higher LCAT (+23%; p < 0.0001) and CETP (+49%; p < 0.0001) activity in AAA sera. HDL ABCG1-CEC was lower (−16%; p < 0.001) and ABCA1-CEC was higher (+31.7%; p < 0.0001) in AAA. Stratification suggests that smoking may partly contribute to these modifications. CEC and CETP activity correlated with CLC only in AAA. CONCLUSIONS: We demonstrated that compared to patients with stenotic atherosclerosis, patients with AAA had altered HDL metabolism and functions involved in their anti-inflammatory and tissue repair activity, particularly through the ABCG1-related intracellular signaling. Clarifying the relevance of this mechanism for AAA evolution might help in developing new diagnostic parameters and therapeutic targets for the early management of this condition. Frontiers Media S.A. 2022-09-12 /pmc/articles/PMC9510680/ /pubmed/36172376 http://dx.doi.org/10.3389/fimmu.2022.935241 Text en Copyright © 2022 Adorni, Palumbo, Marchi, Zimetti, Ossoli, Turri, Bernini, Hollan, Moláček, Treska and Ronda https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Adorni, Maria Pia Palumbo, Marcella Marchi, Cinzia Zimetti, Francesca Ossoli, Alice Turri, Marta Bernini, Franco Hollan, Ivana Moláček, Jiří Treska, Vladislav Ronda, Nicoletta HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
title | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
title_full | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
title_fullStr | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
title_full_unstemmed | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
title_short | HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
title_sort | hdl metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510680/ https://www.ncbi.nlm.nih.gov/pubmed/36172376 http://dx.doi.org/10.3389/fimmu.2022.935241 |
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