Summary of Study ST003524

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002168. The data can be accessed directly via it's Project DOI: 10.21228/M8CR8X This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST003524
Study Title	Arachidonic acid fuels inflammation by unlocking 5-LOX in macrophages after myocardial infarction
Study Summary	An overactive inflammatory response and immune cell infiltration in myocardial infarction (MI) impairs tissue repair. Arachidonic acid (AA) metabolites act as important sources of inflammatory mediators in cardiac tissue. We investigated the mechanisms underlying the AA cascade-mediated inflammatory response after MI. Metabolomics analyses revealed that the 5-lipoxygenase (5-LOX)-dependent AA metabolic pathway derivative leukotriene B4 (LTB4) accumulated in large quantities after MI. Elevated levels of AA in vivo after MI facilitated the recruitment of protein phosphatase 5 (PP5) into the nucleus by binding PP5 to its nuclear transporter receptor karyopherin subunit alpha 1. On entering the nucleus, PP5 directly dephosphorylated 5-LOX at Thr218, promoting the production of the proinflammatory mediator LTB4 by macrophages. Transgenic mice were created with a population of cardiac resident macrophages with a mutation at 5-LOX Thr218. Single-cell transcriptomics showed that these cells overexpressed CXC-chemokine ligand 13 and actively recruited B cells to the heart, exacerbating tissue inflammation. In a UK Biobank cohort, the PP5 E76D mutation was found to be associated with complications after acute MI. Overall, our results have elucidated a conserved role for 5-LOX-phosphorylation-regulated LTB4 levels in MI and identified PP5 as a potential therapeutic target for the treatment of MI.
Institute	Tianjin Medical University
Last Name	Song
First Name	Jiawei
Address	Tianjin Medical University, Tianjin, China., Tianjin, Tianjin, 300070, China
Email	sjw808@tmu.edu.cn
Phone	15309216256
Submit Date	2024-10-14
Raw Data Available	Yes
Raw Data File Type(s)	mzML
Analysis Type Detail	LC-MS
Release Date	2025-11-14
Release Version	1

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Project:

Project ID:	PR002168
Project DOI:	doi: 10.21228/M8CR8X
Project Title:	Arachidonic acid fuels inflammation by unlocking 5-LOX in macrophages after myocardial infarction to promote cardiac dysfunction
Project Summary:	An overactive inflammatory response and immune cell infiltration in myocardial infarction (MI) impairs tissue repair. Arachidonic acid (AA) metabolites act as important sources of inflammatory mediators in cardiac tissue. We investigated the mechanisms underlying the AA cascade-mediated inflammatory response after MI. Metabolomics analyses revealed that the 5-lipoxygenase (5-LOX)-dependent AA metabolic pathway derivative leukotriene B4 (LTB4) accumulated in large quantities after MI. Elevated levels of AA in vivo after MI facilitated the recruitment of protein phosphatase 5 (PP5) into the nucleus by binding PP5 to its nuclear transporter receptor karyopherin subunit alpha 1. On entering the nucleus, PP5 directly dephosphorylated 5-LOX at Thr218, promoting the production of the proinflammatory mediator LTB4 by macrophages. Transgenic mice were created with a population of cardiac resident macrophages with a mutation at 5-LOX Thr218. Single-cell transcriptomics showed that these cells overexpressed CXC-chemokine ligand 13 and actively recruited B cells to the heart, exacerbating tissue inflammation. In a UK Biobank cohort, the PP5 E76D mutation was found to be associated with complications after acute MI. Overall, our results have elucidated a conserved role for 5-LOX-phosphorylation-regulated LTB4 levels in MI and identified PP5 as a potential therapeutic target for the treatment of MI.
Institute:	Tianjin Medical University
Last Name:	Song
First Name:	Jiawei
Address:	Tianjin Medical University, Tianjin, China., Tianjin, Tianjin, 300070, China
Email:	sjw808@tmu.edu.cn
Phone:	15309216256

Subject:

Subject ID:	SU003653
Subject Type:	Human
Subject Species:	Homo sapiens
Taxonomy ID:	9606
Species Group:	Mammals

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id	local_sample_id	treatment
SA386894	C66	Control
SA386895	C75	Control
SA386896	C74	Control
SA386897	C73	Control
SA386898	C72	Control
SA386899	C71	Control
SA386900	C70	Control
SA386901	C69	Control
SA386902	C68	Control
SA386903	C67	Control
SA386904	C65	Control
SA386905	C77	Control
SA386906	C64	Control
SA386907	C63	Control
SA386908	C62	Control
SA386909	C61	Control
SA386910	C60	Control
SA386911	C59	Control
SA386912	C58	Control
SA386913	C57	Control
SA386914	C56	Control
SA386915	C55	Control
SA386916	C76	Control
SA386917	C78	Control
SA386918	C53	Control
SA386919	C91	Control
SA386920	C2	Control
SA386921	C100	Control
SA386922	C99	Control
SA386923	C98	Control
SA386924	C97	Control
SA386925	C96	Control
SA386926	C95	Control
SA386927	C94	Control
SA386928	C93	Control
SA386929	C92	Control
SA386930	C90	Control
SA386931	C79	Control
SA386932	C89	Control
SA386933	C88	Control
SA386934	C87	Control
SA386935	C86	Control
SA386936	C85	Control
SA386937	C84	Control
SA386938	C83	Control
SA386939	C82	Control
SA386940	C81	Control
SA386941	C80	Control
SA386942	C54	Control
SA386943	C1	Control
SA386944	C52	Control
SA386945	C14	Control
SA386946	C24	Control
SA386947	C23	Control
SA386948	C22	Control
SA386949	C21	Control
SA386950	C20	Control
SA386951	C19	Control
SA386952	C18	Control
SA386953	C17	Control
SA386954	C16	Control
SA386955	C15	Control
SA386956	C13	Control
SA386957	C26	Control
SA386958	C12	Control
SA386959	C11	Control
SA386960	C10	Control
SA386961	C9	Control
SA386962	C8	Control
SA386963	C6	Control
SA386964	C5	Control
SA386965	C4	Control
SA386966	C51	Control
SA386967	C3	Control
SA386968	C25	Control
SA386969	C7	Control
SA386970	C27	Control
SA386971	C40	Control
SA386972	C28	Control
SA386973	C50	Control
SA386974	C48	Control
SA386975	C46	Control
SA386976	C45	Control
SA386977	C44	Control
SA386978	C43	Control
SA386979	C42	Control
SA386980	C41	Control
SA386981	C47	Control
SA386982	C39	Control
SA386983	C32	Control
SA386984	C29	Control
SA386985	C38	Control
SA386986	C30	Control
SA386987	C31	Control
SA386988	C49	Control
SA386989	C37	Control
SA386990	C34	Control
SA386991	C35	Control
SA386992	C36	Control
SA386993	C33	Control

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Collection:

Collection ID:	CO003646
Collection Summary:	Plasma samples from 100 non-MI controls and 172 MI patients were collected from Tongji Medical College of Huazhong University of Science and Technology.
Sample Type:	blood(plasma)
Storage Conditions:	-80℃

Treatment:

Treatment ID:	TR003662
Treatment Summary:	No treatment

Sample Preparation:

Sampleprep ID:	SP003660
Sampleprep Summary:	An equivalent volume of human plasma was extracted using a centrifuge tube with low adsorption properties after adding 1 µl of internal standard mixture. AA metabolites were extracted with methanol and ethyl acetate under low light conditions. The extracted samples were evaporated to dryness in a gentle stream of nitrogen, after which the samples were dissolved in 30% acetonitrile. Chromatographic separation was performed on an UPLC BEH C18column (1.7 µm, 100 × 2.1 mm i.d). AA metabolites were analyzed using a QTRAP 5500 Hybrid Triple Quadrupole Linear Ion Trap Mass Spectrometer equipped with a Turbo Ion Spray Electrospray Ion Source.

Sampleprep ID:

SP003660

Sampleprep Summary:

An equivalent volume of human plasma was extracted using a centrifuge tube with low adsorption properties after adding 1 µl of internal standard mixture. AA metabolites were extracted with methanol and ethyl acetate under low light conditions. The extracted samples were evaporated to dryness in a gentle stream of nitrogen, after which the samples were dissolved in 30% acetonitrile. Chromatographic separation was performed on an UPLC BEH C18column (1.7 µm, 100 × 2.1 mm i.d). AA metabolites were analyzed using a QTRAP 5500 Hybrid Triple Quadrupole Linear Ion Trap Mass Spectrometer equipped with a Turbo Ion Spray Electrospray Ion Source.

Chromatography:

Chromatography ID:	CH004392
Instrument Name:	Waters Acquity
Column Name:	Waters ACQUITY UPLC BEH C18 (50 x 2.1mm,1.7um)
Column Temperature:	25
Flow Gradient:	0-3min,30%B; 3-20min,30%B-60%B; 20-24min, 60%B-80%B; 24-27min,80%B; 27-29min,80%B-30%B; 29-30min,30%B
Flow Rate:	0.25mL/min
Solvent A:	100% water; 0.02% acetic acid
Solvent B:	100% acetonitrile
Chromatography Type:	Reversed phase

Analysis:

Analysis ID:	AN005787
Analysis Type:	MS
Chromatography ID:	CH004392
Num Factors:	2
Num Metabolites:	31
Units:	ng/mL