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...

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Detalhes bibliográficos
Autores: Canyelles, Marina|||0000-0002-0278-5337, García Osuna, Álvaro|||0000-0002-6682-0226, Junza, Alexandra, Yanes, Oscar|||0000-0003-3695-7157, Puig Grifol, Núria|||0000-0002-4699-3162, Ordóñez, J. (Jordi)|||0000-0003-4896-5832, Sionis, Alessandro|||0000-0003-0843-9512, Sans-Roselló, Jordi|||0000-0003-3176-6191, Alquézar-Arbé, A.|||0000-0003-4164-274X, Santos, David|||0000-0003-1157-4969, Rotllan, Noemi|||0000-0002-0587-8045, Julve i Gil, Josep|||0000-0002-6531-2246, Tondo Colomer, Mireia|||0000-0002-0301-9984, Escolà-Gil, Joan Carles|||0000-0001-9021-2485, Blanco Vaca, Francisco|||0000-0001-7380-5385
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:269616
Acesso em linha:https://ddd.uab.cat/record/269616
https://dx.doi.org/urn:doi:10.3390/biomedicines9101336
Access Level:acceso abierto
Palavra-chave:HDL-mediated efflux
Macrophages
Trimethylamine N-oxide
Trimethyllysine
Myocardial infarction
Descrição
Resumo: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.

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