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The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction
Impaired HDL-mediated macrophage cholesterol efflux and higher circulating concentrations of trimethylamine N-oxide (TMAO) levels are independent risk factors for cardiovascular mortality. The TMAO precursors, γ-butyrobetaine (γBB) and Trimethyllysine (TML), have also been recently associated with c...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533386/ https://www.ncbi.nlm.nih.gov/pubmed/34680453 http://dx.doi.org/10.3390/biomedicines9101336 |
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author | Canyelles, Marina García-Osuna, Álvaro Junza, Alexandra Yanes, Oscar Puig, Núria Ordóñez-Llanos, Jordi Sionis, Alessandro Sans-Roselló, Jordi Alquézar-Arbé, Aitor Santos, David Rotllan, Noemi Julve, Josep Tondo, Mireia Escolà-Gil, Joan Carles Blanco-Vaca, Francisco |
author_facet | Canyelles, Marina García-Osuna, Álvaro Junza, Alexandra Yanes, Oscar Puig, Núria Ordóñez-Llanos, Jordi Sionis, Alessandro Sans-Roselló, Jordi Alquézar-Arbé, Aitor Santos, David Rotllan, Noemi Julve, Josep Tondo, Mireia Escolà-Gil, Joan Carles Blanco-Vaca, Francisco |
author_sort | Canyelles, Marina |
collection | PubMed |
description | Impaired HDL-mediated macrophage cholesterol efflux and higher circulating concentrations of trimethylamine N-oxide (TMAO) levels are independent risk factors for cardiovascular mortality. The TMAO precursors, γ-butyrobetaine (γBB) and Trimethyllysine (TML), have also been recently associated with cardiovascular death, but their interactions with HDL-mediated cholesterol efflux remain unclear. We aimed to determine the associations between APOB depleted plasma-mediated macrophage cholesterol efflux and plasma TMAO, γBB, and TML concentrations and explore their association with two-year follow-up mortality in patients with acute ST-elevation myocardial infarction (STEMI) and unstable angina (UA). Baseline and ATP-binding cassette transporter ABCA1 and ABCG1 (ABCA1/G1)-mediated macrophage cholesterol efflux to APOB-depleted plasma was decreased in patients with STEMI, and the latter was further impaired in those who died during follow-up. Moreover, the circulating concentrations of TMAO, γBB, and TML were higher in the deceased STEMI patients when compared with the STEMI survivors or UA patients. However, after statistical adjustment, only ABCA1/G1-mediated macrophage cholesterol efflux remained significantly associated with mortality. Furthermore, neither the TMAO, γBB, nor TML levels altered the HDL-mediated macrophage cholesterol efflux in vitro. We conclude that impaired ABCA1/G1-mediated macrophage cholesterol efflux is independently associated with mortality at follow-up in STEMI patients. |
format | Online Article Text |
id | pubmed-8533386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85333862021-10-23 The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction Canyelles, Marina García-Osuna, Álvaro Junza, Alexandra Yanes, Oscar Puig, Núria Ordóñez-Llanos, Jordi Sionis, Alessandro Sans-Roselló, Jordi Alquézar-Arbé, Aitor Santos, David Rotllan, Noemi Julve, Josep Tondo, Mireia Escolà-Gil, Joan Carles Blanco-Vaca, Francisco Biomedicines Article Impaired HDL-mediated macrophage cholesterol efflux and higher circulating concentrations of trimethylamine N-oxide (TMAO) levels are independent risk factors for cardiovascular mortality. The TMAO precursors, γ-butyrobetaine (γBB) and Trimethyllysine (TML), have also been recently associated with cardiovascular death, but their interactions with HDL-mediated cholesterol efflux remain unclear. We aimed to determine the associations between APOB depleted plasma-mediated macrophage cholesterol efflux and plasma TMAO, γBB, and TML concentrations and explore their association with two-year follow-up mortality in patients with acute ST-elevation myocardial infarction (STEMI) and unstable angina (UA). Baseline and ATP-binding cassette transporter ABCA1 and ABCG1 (ABCA1/G1)-mediated macrophage cholesterol efflux to APOB-depleted plasma was decreased in patients with STEMI, and the latter was further impaired in those who died during follow-up. Moreover, the circulating concentrations of TMAO, γBB, and TML were higher in the deceased STEMI patients when compared with the STEMI survivors or UA patients. However, after statistical adjustment, only ABCA1/G1-mediated macrophage cholesterol efflux remained significantly associated with mortality. Furthermore, neither the TMAO, γBB, nor TML levels altered the HDL-mediated macrophage cholesterol efflux in vitro. We conclude that impaired ABCA1/G1-mediated macrophage cholesterol efflux is independently associated with mortality at follow-up in STEMI patients. MDPI 2021-09-27 /pmc/articles/PMC8533386/ /pubmed/34680453 http://dx.doi.org/10.3390/biomedicines9101336 Text en © 2021 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 | Article Canyelles, Marina García-Osuna, Álvaro Junza, Alexandra Yanes, Oscar Puig, Núria Ordóñez-Llanos, Jordi Sionis, Alessandro Sans-Roselló, Jordi Alquézar-Arbé, Aitor Santos, David Rotllan, Noemi Julve, Josep Tondo, Mireia Escolà-Gil, Joan Carles Blanco-Vaca, Francisco The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction |
title | The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction |
title_full | The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction |
title_fullStr | The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction |
title_full_unstemmed | The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction |
title_short | The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction |
title_sort | capacity of apob-depleted plasma in inducing atp-binding cassette a1/g1-mediated macrophage cholesterol efflux—but not gut microbial-derived metabolites—is independently associated with mortality in patients with st-segment elevation myocardial infarction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533386/ https://www.ncbi.nlm.nih.gov/pubmed/34680453 http://dx.doi.org/10.3390/biomedicines9101336 |
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