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 infar

Identifier:  imarina:9229577

Handle: https://hdl.handle.net/20.500.11797/imarina9229577

Authors:  Canyelles, Marina; Garcia-Osuna, Alvaro; Junza, Alexandra; Yanes, Oscar; Puig, Nuria; Ordonez-Llanos, Jordi; Sionis, Alessandro; Sans-Rosello, Jordi; Alquezar-Arbe, Aitor; Santos, David; Rotllan, Noemi; Julve, Josep; Tondo, Mireia; Escola-Gil, Joan Carles; Blanco-Vaca, Francisco

Abstract:
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.