1d27539d200ac66d49141cf8907a77af 269616.pdf 0af58a554f2151a11aae63b084cac82ae9bbcf84 269616.pdf 3d2da0dfd39ea551baaae54c84063ef6b5ad7f61e379cdfbcfbcc112c142ffce 269616.pdf 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 Subject: 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, -butyrobetaine (BB) 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, BB, 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, BB, 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, BB, 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. Keywords: HDL-mediated efflux; macrophages; trimethylamine N-oxide; trimethyllysine; myocardial infarction Author: Marina Canyelles, Álvaro García-Osuna, Alexandra Junza, Oscar Yanes, Núria Puig, Jordi Ordóñez-Llanos, Alessandro Sionis, Jordi Sans-Roselló, Aitor Alquézar-Arbé, David Santos, Noemi Rotllan, Josep Julve, Mireia Tondo, Joan Carles Escolà-Gil and Francisco Blanco-Vaca Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Sep 29 08:55:44 2021 CEST ModDate: Wed Sep 29 10:03:50 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 867170 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OHKNFJ+VnURWPalladioL Type 1 Custom yes yes no 10 0 QNWFPZ+EURM10 Type 1 Builtin yes yes no 15 0 PWSRZS+URWPalladioL-Ital Type 1 Custom yes yes no 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(2019-04-17) LastModified: 2023-03-31 12:04:38 CEST Size: 867170 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 389 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Experimental Section Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Population and Data Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Blood Samples and Biochemical Measurements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Ex Vivo and In Vitro Cholesterol Efflux Capacity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Plasma TMAO, BB and TML Determinations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Statistical Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Study Subjects Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: ABCA1 and ABCG1-Mediated Macrophage Cholesterol Efflux to APOB-Fepleted Serum Ex Vivo Is Down Regulated in Deceased STEMI Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Circulating Levels of TMAO, BB, and TML Are Increased in STEMI Patients Who Died during Follow-Up Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: ABCA1/G1-Mediated Macrophage Cholesterol Efflux Is Independently Associated with Mortality Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: TMAO, BB, and TML Did Not Affect APOB-Depleted Plasma-Mediated Macrophage Cholesterol Efflux In Vitro Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: 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 Author: Marina Canyelles, Álvaro García-Osuna, Alexandra Junza, Oscar Yanes, Núria Puig, Jordi Ordóñez-Llanos, Alessandro Sionis, Jordi Sans-Roselló, Aitor Alquézar-Arbé, David Santos, Noemi Rotllan, Josep Julve, Mireia Tondo, Joan Carles Escolà-Gil and Francisco Blanco-Vaca Subject: 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, -butyrobetaine (BB) 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, BB, 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, BB, 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, BB, 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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