489153f7091a452ed62aa3ab001bd572 pmc_8911412.pdf 6141b3ea535afe99e48bdd7b4a52cd57466a5f3b pmc_8911412.pdf e2a0e61624e1600d7fcf48d989320c19f2b41c667d050a0f1cf750bc6186253c pmc_8911412.pdf Title: TMAO and Gut Microbial-Derived Metabolites TML and BB Are Not Associated with Thrombotic Risk in Patients with Venous Thromboembolism Subject: Background: The present work evaluates the association between circulating concentrations of Trimethylamine-N-oxide (TMAO), gamma butyrobetaine (BB), and trimetyllisine (TML) in controls and patients with venous thromboembolism (VTE) with coagulation parameters. Methods: The study involved 54 VTE patients and 57 controls. Platelet function, platelet hyperreactivity, platelet adhesiveness, thrombosis-associated parameters, and thrombin generation parameters were studied. Plasma TMAO, BB, and TML determination was performed using an ultra-high-performance liquid chromatography system coupled with mass spectrometry. Results: No differences were found for TMAO, BB, or TML concentrations between controls and VTE patients. In thrombin generation tests, TMAO, BB, and TML showed a positive correlation with lag time and time to peak. TMAO, BB, and TML negatively correlated with peak height. No significant differences were observed regarding TMAO, BB, and TML concentrations between the two blood withdrawals, nor when the control and VTE patients were analyzed separately. No correlation was observed between these gut metabolites and platelet function parameters. Conclusions: No differences were found regarding TMAO, BB, and TML concentrations between the control and VTE groups. Some correlations were found; however, they were mild or went in the opposite direction of what would be expected if TMAO and its derivatives were related to VTE risk. Keywords: trimethylamine N-oxide; TMAO; BB; TML; liquid chromatography–mass spectrometry; venous thromboembolism Author: Marina Canyelles, Melania Plaza, Noemí Rotllan, Dolors Llobet, Josep Julve, Sergi Mojal, Maribel Diaz-Ricart, José Manuel Soria, Joan Carles Escolà-Gil, Mireia Tondo, Francisco Blanco-Vaca and Joan Carles Souto Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Mar 7 09:00:38 2022 CET ModDate: Mon Mar 7 09:02:32 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1192785 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- AKXRSZ+EURB10 Type 1 Builtin yes yes no 10 0 GGHKEL+VnURWPalladioL-Bold Type 1 Custom yes yes no 14 0 HKBJPQ+VnURWPalladioL Type 1 Custom yes yes no 19 0 OQIVQT+EURM10 Type 1 Builtin yes yes no 23 0 EFMZNK+URWPalladioL-Bold Type 1 Custom yes yes no 27 0 FBJFDB+URWPalladioL-Roma Type 1 Custom yes yes no 32 0 YKSIOD+URWPalladioL-Ital Type 1 Custom yes yes no 36 0 RUWDWW+EURM7 Type 1 Builtin yes yes no 40 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 48 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 52 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 56 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 68 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 71 0 VIWIOF+CMSY10 Type 1 Builtin yes yes no 96 0 GEWEQC+PazoMath-Italic Type 1 Builtin yes yes no 103 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 110 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-05-19 02:40:20 CEST RepresentationInformation: pmc_8911412.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-03-28 07:26:02 CEST Size: 1192785 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 255 FreeObjects: 3 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4923ab24 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Study Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Coagulation Parameters Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Platelet Function Analysis (PFA) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Platelet Hyperreactivity (PHR) Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Platelet Adhesiveness (PA) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Thrombosis-Associated Parameters Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Thrombin Generation Parameters Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Plasma TMAO, BB, and TML Determination Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Children: Item: Title: Study Cohort Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Gut-Related Metabolites and VTE Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Gut-Related Metabolites and Coagulation Parameters Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Gut-Derived Metabolites over Time Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Info: Title: TMAO and Gut Microbial-Derived Metabolites TML and BB Are Not Associated with Thrombotic Risk in Patients with Venous Thromboembolism Author: Marina Canyelles, Melania Plaza, Noemí Rotllan, Dolors Llobet, Josep Julve, Sergi Mojal, Maribel Diaz-Ricart, José Manuel Soria, Joan Carles Escolà-Gil, Mireia Tondo, Francisco Blanco-Vaca and Joan Carles Souto Subject: Background: The present work evaluates the association between circulating concentrations of Trimethylamine-N-oxide (TMAO), gamma butyrobetaine (BB), and trimetyllisine (TML) in controls and patients with venous thromboembolism (VTE) with coagulation parameters. Methods: The study involved 54 VTE patients and 57 controls. Platelet function, platelet hyperreactivity, platelet adhesiveness, thrombosis-associated parameters, and thrombin generation parameters were studied. Plasma TMAO, BB, and TML determination was performed using an ultra-high-performance liquid chromatography system coupled with mass spectrometry. Results: No differences were found for TMAO, BB, or TML concentrations between controls and VTE patients. In thrombin generation tests, TMAO, BB, and TML showed a positive correlation with lag time and time to peak. TMAO, BB, and TML negatively correlated with peak height. No significant differences were observed regarding TMAO, BB, and TML concentrations between the two blood withdrawals, nor when the control and VTE patients were analyzed separately. No correlation was observed between these gut metabolites and platelet function parameters. Conclusions: No differences were found regarding TMAO, BB, and TML concentrations between the control and VTE groups. Some correlations were found; however, they were mild or went in the opposite direction of what would be expected if TMAO and its derivatives were related to VTE risk. 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