#METABOLOMICS WORKBENCH lvhuizhen_20240225_234135 DATATRACK_ID:4674 STUDY_ID:ST003244 ANALYSIS_ID:AN005314 PROJECT_ID:PR002014 VERSION 1 CREATED_ON June 7, 2024, 11:12 am #PROJECT PR:PROJECT_TITLE Suppression of prostaglandin I2–type I interferon axis induces extramedullary PR:PROJECT_TITLE hematopoiesis to promote cardiac repair after myocardial infarction PR:PROJECT_SUMMARY Background: Immune cells are closely associated with all processes of cardiac PR:PROJECT_SUMMARY repair following myocardial infarction (MI), including the initiation, PR:PROJECT_SUMMARY development, and resolution of inflammation. Spleen extramedullary hematopoiesis PR:PROJECT_SUMMARY (EMH) serves as a critical source of emergency mature blood cells that are PR:PROJECT_SUMMARY generated through the self-renewal and differentiation of hematopoietic PR:PROJECT_SUMMARY stem/progenitor cells (HSPCs). However, how EMH responds to MI and the role of PR:PROJECT_SUMMARY EMH in cardiac repair post-MI remains unclear. Methods: To assess the role of PR:PROJECT_SUMMARY spleen EMH in MI, a Tcf21CreERScfflox/flox MI mouse model with inhibited EMH was PR:PROJECT_SUMMARY constructed. GFP+ HSCs sorted from eGFP mouse spleen by flow cytometry and PR:PROJECT_SUMMARY injected into Tcf21CreERScfflox/flox mice to test the sources of local PR:PROJECT_SUMMARY inflammatory cells during MI. Using highly specific liquid chromatography-tandem PR:PROJECT_SUMMARY mass spectrometry and single-cell RNA sequencing, we analyzed the lipidomic PR:PROJECT_SUMMARY profile of arachidonic acid metabolites and the transcriptomes of HSPCs in the PR:PROJECT_SUMMARY spleen after MI. Results: We found that MI enhanced EMH, as reflected by the PR:PROJECT_SUMMARY increase in spleen weight and volume and the number of HSPCs in the spleen. The PR:PROJECT_SUMMARY lack of EMH in Scf-deficient mice exacerbated tissue injury post-MI. Analyzing PR:PROJECT_SUMMARY the transcriptome of spleen HSPCs post-MI, we found the type I interferon (IFN) PR:PROJECT_SUMMARY pathway significantly inhibited in HSC/multipotent progenitor subclusters and PR:PROJECT_SUMMARY the absence of type I IFN signaling enhanced the MI-induced spleen EMH. PR:PROJECT_SUMMARY Lipidomics analysis revealed that prostaglandin I2 (PGI2) was markedly reduced PR:PROJECT_SUMMARY in the spleen. Mechanistically, PGI2 suppressed MI-induced EMH through a PGI2 PR:PROJECT_SUMMARY receptor (IP)-cAMP-453p-SP1 cascade in spleen HSPCs. Finally, hematopoietic PR:PROJECT_SUMMARY cell-specific IP-deficient mice exhibited enhanced EMH and improved cardiac PR:PROJECT_SUMMARY recovery post-MI, which mitigated the adverse secondary outcomes of treatment PR:PROJECT_SUMMARY with cicaprost, a PGI2 analog and anti-inflammatory agent. Conclusions: PR:PROJECT_SUMMARY Together, our findings revealed that a PGI2–IFN axis was involved in spleen PR:PROJECT_SUMMARY EMH after MI, providing new mechanistic insights into spleen EMH post-MI and PR:PROJECT_SUMMARY offering a new therapeutic target for treating ischemic cardiac injury. PR:INSTITUTE Tianjin Medical University PR:LABORATORY Metabolic cardiovascular disease lab PR:LAST_NAME Lv PR:FIRST_NAME Huizhen PR:ADDRESS Qixiangtai Road 22th, Tianjin, Tianjin, 300070, China PR:EMAIL lvhuizhen@tmu.edu.cn PR:PHONE 83336591 #STUDY ST:STUDY_TITLE Suppression of prostaglandin I2–type I interferon axis induces extramedullary ST:STUDY_TITLE hematopoiesis to promote cardiac repair after myocardial infarction ST:STUDY_SUMMARY Background: Immune cells are closely associated with all processes of cardiac ST:STUDY_SUMMARY repair following myocardial infarction (MI), including the initiation, ST:STUDY_SUMMARY development, and resolution of inflammation. Spleen extramedullary hematopoiesis ST:STUDY_SUMMARY (EMH) serves as a critical source of emergency mature blood cells that are ST:STUDY_SUMMARY generated through the self-renewal and differentiation of hematopoietic ST:STUDY_SUMMARY stem/progenitor cells (HSPCs). However, how EMH responds to MI and the role of ST:STUDY_SUMMARY EMH in cardiac repair post-MI remains unclear. Methods: To assess the role of ST:STUDY_SUMMARY spleen EMH in MI, a Tcf21CreERScfflox/flox MI mouse model with inhibited EMH was ST:STUDY_SUMMARY constructed. GFP+ HSCs sorted from eGFP mouse spleen by flow cytometry and ST:STUDY_SUMMARY injected into Tcf21CreERScfflox/flox mice to test the sources of local ST:STUDY_SUMMARY inflammatory cells during MI. Using highly specific liquid chromatography-tandem ST:STUDY_SUMMARY mass spectrometry and single-cell RNA sequencing, we analyzed the lipidomic ST:STUDY_SUMMARY profile of arachidonic acid metabolites and the transcriptomes of HSPCs in the ST:STUDY_SUMMARY spleen after MI. Results: We found that MI enhanced EMH, as reflected by the ST:STUDY_SUMMARY increase in spleen weight and volume and the number of HSPCs in the spleen. The ST:STUDY_SUMMARY lack of EMH in Scf-deficient mice exacerbated tissue injury post-MI. Analyzing ST:STUDY_SUMMARY the transcriptome of spleen HSPCs post-MI, we found the type I interferon (IFN) ST:STUDY_SUMMARY pathway significantly inhibited in HSC/multipotent progenitor subclusters and ST:STUDY_SUMMARY the absence of type I IFN signaling enhanced the MI-induced spleen EMH. ST:STUDY_SUMMARY Lipidomics analysis revealed that prostaglandin I2 (PGI2) was markedly reduced ST:STUDY_SUMMARY in the spleen. Mechanistically, PGI2 suppressed MI-induced EMH through a PGI2 ST:STUDY_SUMMARY receptor (IP)-cAMP-453p-SP1 cascade in spleen HSPCs. Finally, hematopoietic ST:STUDY_SUMMARY cell-specific IP-deficient mice exhibited enhanced EMH and improved cardiac ST:STUDY_SUMMARY recovery post-MI, which mitigated the adverse secondary outcomes of treatment ST:STUDY_SUMMARY with cicaprost, a PGI2 analog and anti-inflammatory agent. Conclusions: ST:STUDY_SUMMARY Together, our findings revealed that a PGI2–IFN axis was involved in spleen ST:STUDY_SUMMARY EMH after MI, providing new mechanistic insights into spleen EMH post-MI and ST:STUDY_SUMMARY offering a new therapeutic target for treating ischemic cardiac injury. ST:INSTITUTE Tianjin Medical University ST:LAST_NAME Lv ST:FIRST_NAME Huizhen ST:ADDRESS Qixiangtai Road 22th, Tianjin, Tianjin, 300070, China ST:EMAIL lvhuizhen@tmu.edu.cn ST:PHONE 13212161520 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #FACTORS #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS - Sham-1 Sample source:Spleen | treatment:Sham RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-1 SUBJECT_SAMPLE_FACTORS - Sham-2 Sample source:Spleen | treatment:Sham RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-2 SUBJECT_SAMPLE_FACTORS - Sham-3 Sample source:Spleen | treatment:Sham RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-3 SUBJECT_SAMPLE_FACTORS - Sham-4 Sample source:Spleen | treatment:Sham RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-4 SUBJECT_SAMPLE_FACTORS - Sham-5 Sample source:Spleen | treatment:Sham RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-5 SUBJECT_SAMPLE_FACTORS - Sham-6 Sample source:Spleen | treatment:Sham RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-6 SUBJECT_SAMPLE_FACTORS - Sham-7 Sample source:Spleen | treatment:Sham RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-7 SUBJECT_SAMPLE_FACTORS - Sham-8 Sample source:Spleen | treatment:Sham RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-8 SUBJECT_SAMPLE_FACTORS - Sham-9 Sample source:Spleen | treatment:Sham RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-9 SUBJECT_SAMPLE_FACTORS - MI 1d-1 Sample source:Spleen | treatment:MI1d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-10 SUBJECT_SAMPLE_FACTORS - MI 1d-2 Sample source:Spleen | treatment:MI1d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-11 SUBJECT_SAMPLE_FACTORS - MI 1d-3 Sample source:Spleen | treatment:MI1d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-12 SUBJECT_SAMPLE_FACTORS - MI 1d-4 Sample source:Spleen | treatment:MI1d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-13 SUBJECT_SAMPLE_FACTORS - MI 1d-5 Sample source:Spleen | treatment:MI1d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-14 SUBJECT_SAMPLE_FACTORS - MI 1d-6 Sample source:Spleen | treatment:MI1d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-15 SUBJECT_SAMPLE_FACTORS - MI 1d-7 Sample source:Spleen | treatment:MI1d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-16 SUBJECT_SAMPLE_FACTORS - MI 1d-8 Sample source:Spleen | treatment:MI1d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-17 SUBJECT_SAMPLE_FACTORS - MI 1d-9 Sample source:Spleen | treatment:MI1d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-18 SUBJECT_SAMPLE_FACTORS - MI 3d-1 Sample source:Spleen | treatment:MI 3d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-19 SUBJECT_SAMPLE_FACTORS - MI 3d-2 Sample source:Spleen | treatment:MI 3d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-20 SUBJECT_SAMPLE_FACTORS - MI 3d-3 Sample source:Spleen | treatment:MI 3d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-21 SUBJECT_SAMPLE_FACTORS - MI 3d-4 Sample source:Spleen | treatment:MI 3d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-22 SUBJECT_SAMPLE_FACTORS - MI 3d-5 Sample source:Spleen | treatment:MI 3d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-23 SUBJECT_SAMPLE_FACTORS - MI 3d-6 Sample source:Spleen | treatment:MI 3d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-24 SUBJECT_SAMPLE_FACTORS - MI 3d-7 Sample source:Spleen | treatment:MI 3d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-25 SUBJECT_SAMPLE_FACTORS - MI 3d-8 Sample source:Spleen | treatment:MI 3d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-26 SUBJECT_SAMPLE_FACTORS - MI 3d-9 Sample source:Spleen | treatment:MI 3d RAW_FILE_NAME( raw data file names)=Data_2_eico_lvhuizhen_48-27 #COLLECTION CO:COLLECTION_SUMMARY Spleen samples from mice subjected to myocardial infarction (MI) surgery were CO:COLLECTION_SUMMARY extracted with liquid–liquid extraction. CO:SAMPLE_TYPE Spleen CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY No treatment #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 50 mg of spleen tissues was homogenized with methanol (2% formic acid and 0.01 SP:SAMPLEPREP_SUMMARY mol/L BHT) spiked with internal standard mixture. After centrifugation, the SP:SAMPLEPREP_SUMMARY supernatant was added to water and ethylacetate, and the sample was mixed and SP:SAMPLEPREP_SUMMARY centrifuged at 12,000 × g. The upper organic phase was transferred to a new SP:SAMPLEPREP_SUMMARY tube, and the water phase was extracted again. The organic phase was combined SP:SAMPLEPREP_SUMMARY and then evaporated to dryness and further dissolved in 100 μL of 30% SP:SAMPLEPREP_SUMMARY acetonitrile. After vigorous mixing, samples were filtered by use of centrifuge SP:SAMPLEPREP_SUMMARY tube filters (nylon membrane, 0.22 μm). #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Waters Acquity CH:COLUMN_NAME Waters ACQUITY UPLC BEH C18 (50 x 2.1mm,1.7um) CH:SOLVENT_A 100% water; 0.3% ethanoic acid CH:SOLVENT_B 100% acetonitrile CH:FLOW_GRADIENT 0-3min：70%A:30%B，3-20min：40%A:60%B, CH:FLOW_GRADIENT 20-27min：20%A:80%B，27-30min：70%A;30%B CH:FLOW_RATE 0.25mL/min CH:COLUMN_TEMPERATURE 25 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME ABI Sciex 5500 QTrap MS:INSTRUMENT_TYPE QTRAP MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS Arachidonic acid metabolites were quantified by use of a 5500 QTRAP hybrid MS:MS_COMMENTS triple quadrupole linear ion trap mass spectrometer (AB Sciex, Foster City, CA, MS:MS_COMMENTS USA) equipped with a Turbo Ion Spray electrospray ionization source. The mass MS:MS_COMMENTS spectrometer was operated using the software Analyst 1.5.1. Analytes were MS:MS_COMMENTS detected using multiple reaction monitoring (MRM) scans in negative mode. The MS:MS_COMMENTS dwell time used for all MRM experiments was 25 ms. The ion source parameters MS:MS_COMMENTS were set as follows: CUR  =  40 psi, GS1  =  30 psi, GS2  =  30 psi, MS:MS_COMMENTS IS  =  −4500 V, CAD  =  medium, and temp  =  500°C. Metaboanalyst MS:MS_COMMENTS 3.0 (http://www.metaboanalyst.ca) was used for metabolomic data analysis. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS ng/mg of tissue MS_METABOLITE_DATA_START Samples Sham-1 Sham-2 Sham-3 Sham-4 Sham-5 Sham-6 Sham-7 Sham-8 Sham-9 MI 1d-1 MI 1d-2 MI 1d-3 MI 1d-4 MI 1d-5 MI 1d-6 MI 1d-7 MI 1d-8 MI 1d-9 MI 3d-1 MI 3d-2 MI 3d-3 MI 3d-4 MI 3d-5 MI 3d-6 MI 3d-7 MI 3d-8 MI 3d-9 Factors Sample source:Spleen | treatment:Sham Sample source:Spleen | treatment:Sham Sample source:Spleen | treatment:Sham Sample source:Spleen | treatment:Sham Sample source:Spleen | treatment:Sham Sample source:Spleen | treatment:Sham Sample source:Spleen | treatment:Sham Sample source:Spleen | treatment:Sham Sample source:Spleen | treatment:Sham Sample source:Spleen | treatment:MI1d Sample source:Spleen | treatment:MI1d Sample source:Spleen | treatment:MI1d Sample source:Spleen | treatment:MI1d Sample source:Spleen | treatment:MI1d Sample source:Spleen | treatment:MI1d Sample source:Spleen | treatment:MI1d Sample source:Spleen | treatment:MI1d Sample source:Spleen | treatment:MI1d Sample source:Spleen | treatment:MI 3d Sample source:Spleen | treatment:MI 3d Sample source:Spleen | treatment:MI 3d Sample source:Spleen | treatment:MI 3d Sample source:Spleen | treatment:MI 3d Sample source:Spleen | treatment:MI 3d Sample source:Spleen | treatment:MI 3d Sample source:Spleen | treatment:MI 3d Sample source:Spleen | treatment:MI 3d AA_COX_6k-PGF1a 1.05 1.14 1.16 1.20 1.25 1.42 1.52 1.57 1.97 0.25 1.16 1.24 0.25 1.25 1.26 1.28 1.43 0.16 0.08 0.66 0.78 0.07 0.06 0.92 0.94 0.94 1.01 AA_COX_PGD2 2.67 2.02 2.65 2.01 2.69 2.66 2.35 3.20 2.43 0.86 2.60 2.63 0.71 2.78 2.49 2.91 2.55 0.43 0.12 1.55 1.55 0.22 0.14 2.06 2.31 1.99 2.62 AA_COX_15d-PGJ2 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 AA_COX_PGB2 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 AA_COX_PGE2 0.51 0.54 0.62 0.49 0.68 0.39 0.58 0.80 0.71 0.12 0.64 0.63 0.10 0.62 0.62 0.68 0.65 0.06 0.02 0.24 0.30 0.03 0.02 0.44 0.40 0.34 0.55 AA_COX_PGF2a 0.06 0.06 0.08 0.05 0.08 0.06 0.06 0.10 0.06 0.01 0.09 0.07 0.02 0.08 0.08 0.07 0.07 0.01 0.00 0.05 0.04 0.00 0.00 0.09 0.05 0.04 0.06 AA_COX_PGJ2 0.03 0.03 0.02 0.02 0.04 0.02 0.02 0.06 0.02 0.00 0.04 0.04 0.00 0.03 0.02 0.04 0.02 0.00 0.00 0.01 0.01 0.00 0.00 0.02 0.02 0.01 0.04 AA_COX_TXB2 0.23 0.22 0.28 0.21 0.27 0.23 0.24 0.31 0.24 0.06 0.28 0.27 0.06 0.28 0.27 0.31 0.29 0.03 0.01 0.16 0.18 0.02 0.01 0.22 0.21 0.23 0.25 AA_LOX_11-HETE 1.04 0.92 0.82 0.83 1.13 0.96 1.11 1.21 1.27 0.15 1.11 1.18 0.17 1.29 1.52 1.36 1.14 0.10 0.03 0.46 0.43 0.04 0.04 0.86 0.85 0.59 1.15 AA_LOX_12-HETE 3.87 11.80 12.50 4.25 13.59 12.49 10.30 9.74 3.34 0.55 24.46 6.23 0.63 5.11 8.95 5.74 6.51 0.43 0.14 1.72 5.30 0.12 0.10 15.58 6.73 6.27 7.26 AA_LOX_15-HETE 0.98 0.72 0.63 0.77 0.84 0.60 0.94 1.00 0.82 0.15 0.84 0.95 0.25 1.01 1.09 0.95 0.71 0.12 0.05 0.40 0.27 0.05 0.03 0.65 0.63 0.45 0.97 AA_LOX_15-oxo-ETE 0.002409956 0.001532624 0.001613604 0.002338645 0.00170946 0.002797267 0.003836576 0.001952622 0.003850409 0.000357583 0.002055459 0.002515349 0.000738419 0.002101508 0.003487624 0.002644413 0.003946888 0.003213431 0.001946889 0.000626202 0.00096191 0.000162622 0.000971286 0.002619516 0.001551862 0.001223242 0.002172712 AA_LOX_5-HETE 0.027932526 0.037928319 0.202144734 0.043274949 0.06116742 0.041279395 0.063962025 0.060255403 0.026342497 0.023595074 0.069691661 0.052677639 0.055174281 0.034349704 0.039310253 0.046780287 0.060636874 0.065518715 0.046397559 0.037335355 0.042499965 0.038234793 0.03145908 0.061105901 0.039760849 0.062526751 0.055116653 AA_LOX_5-oxo-ETE 0.00101255 0.001971416 0.004525831 0.001034923 0.001269489 0.003380108 0.003643455 0.001513189 0.001319479 0.00086096 0.003422661 0.000767154 0.004564144 0.002150404 0.002049362 0.001288748 0.00489081 0.012040301 0.002800802 0.000901782 0.004436582 0.002752644 0.003162656 0.001579587 0.001343931 0.005464265 0.001900404 AA_LOX_6S-LXA4 0.000145033 0.0000679 0.000249423 0.000118506 0.000164676 0.000173091 0.000181115 0.000216246 0.000144219 0.0000523 0.000066 0.00013944 0.000126383 0.000124849 0.000227307 0.000140048 0.000161348 0.000138304 0.0000799 0.0000819 0.000121096 0.0000939 0.0000502 0.000098 0.00013712 0.000066 0.000151197 AA_LOX_8-HETE 0.023744583 0.054924533 0.049023844 0.023575332 0.058353912 0.079289283 0.037813593 0.038950032 0.020088235 0.004768437 0.100543132 0.029971608 0.008991937 0.023104165 0.047885652 0.027674879 0.047394221 0.004543164 0.005969483 0.010421346 0.036828913 0.005307692 0.00182904 0.059795743 0.037086925 0.047452268 0.030240401 AA_LOX_9-HETE 0.007295621 0.011002488 0.008192 0.006119154 0.014340378 0.009365577 0.008594754 0.011371206 0.00799454 0.00288256 0.017195192 0.008236151 0.001014529 0.007524789 0.010816241 0.006776366 0.01262844 0.00241221 0.002396591 0.004969957 0.006334453 0.003066016 0.00517978 0.00813996 0.008289194 0.015963906 0.00631243 AA_LOX_LTB4 0.002271877 0.006051621 0.009203877 0.00397283 0.0101093 0.005690528 0.003176524 0.007841132 0.001455883 0.000234541 0.010274134 0.003015295 0.000800788 0.003344209 0.002783428 0.003591388 0.002315991 0.00048532 0.000214958 0.000966328 0.003333185 0.00035384 0.000120266 0.009043062 0.003094596 0.004526602 0.002801694 AA_P450_11,12 DHET 0.00040079 0.000401592 0.000420748 0.000269552 0.000645826 0.001181929 0.000448872 0.000634598 0.000687993 0.000298442 0.000482548 0.000413823 0.000302653 0.000503133 0.000764535 0.000482428 0.000674604 0.000492168 0.000242351 0.000429024 0.000635374 0.000181805 0.000230282 0.00050755 0.000487258 0.000698179 0.000640395 AA_P450_11,12-EET 0.001683118 0.000609304 0.00056345 0.000093 0.000250702 0.0009142 0.002886204 0.000561975 0.000453411 0.000270243 0.002214996 0.000394409 0.000751391 0.000632992 0.000805489 0.00018057 0.002850797 0.006012438 0.000127464 0.000392109 0.001211135 0.0000523 0.000705238 0.002454158 0.000419311 0.001465909 0.000252531 AA_P450_14,15 DHET 0.000760168 0.001182643 0.000895647 0.001001846 0.001108592 0.001011573 0.001350773 0.001442812 0.001360733 0.000493765 0.001687366 0.00095773 0.000704474 0.001487014 0.00170882 0.001682204 0.001651927 0.000826726 0.000518124 0.000390575 0.001521254 0.000711281 0.000506318 0.001339538 0.000967465 0.001808827 0.001451008 AA_P450_18-HETE 0.001081858 0.000657614 0.000891901 0.001245989 0.000986232 0.001578849 0.000911818 0.00089479 0.001379011 0.000201357 0.001345789 0.001295374 0.000309537 0.001248734 0.002304486 0.000743183 0.002008279 0.000332721 0.000467921 0.000568623 0.001402724 0.00004 0.000332722 0.000963705 0.001740116 0.003126812 0.000571019 AA_P450_5,6 DHET 0.000311983 0.0006921 0.00073283 0.000343147 0.000821177 0.000168613 0.000612264 0.001331133 0.000189608 0.000332599 0.000731727 0.000520814 0.000916645 0.000433882 0.00040085 0.000737963 0.000369149 0.002398183 0.001174243 0.001041785 0.000626279 0.000822585 0.000957739 0.001396468 0.000253932 0.001362183 0.000798327 AA_P450_8,9 DHET 0.000140118 0.000418255 0.00021897 0.000256406 0.000295539 0.000546618 0.000157428 0.000865373 0.000257253 0.0000431 0.000318861 0.000181693 0.000193483 0.000351441 0.000244099 0.000336914 0.00069002 0.000311104 0.00021218 0.000337393 0.000157057 0.000178004 0.000136387 0.000299215 0.000315906 0.00064426 0.000468815 AA_P450_8,9-EET 0.001170465 0.002936516 0.008641766 0.001372076 0.004724973 0.009308307 0.003327657 0.003548665 0.002793081 0.00091554 0.001252152 0.000300729 0.001318327 0.000769279 0.00078899 0.000574555 0.004667413 0.002615436 0.000471854 0.000433034 0.003217061 0.002589999 0.001131542 0.005684427 0.000953105 0.004199676 0.002420551 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Pubchem ID Kegg ID AA_COX_6k-PGF1a 5280888 C05961 AA_COX_PGD2 448457 C00696 AA_COX_15d-PGJ2 5311211 C14717 AA_COX_PGB2 5280881 C05954 AA_COX_PGE2 5280360 C00584 AA_COX_PGF2a 5280363 C00639 AA_COX_PGJ2 5280884 C05957 AA_COX_TXB2 5283137 C05963 AA_LOX_11-HETE 14123410 AA_LOX_12-HETE 13786989 C14777 AA_LOX_15-HETE 9966861 C21482 AA_LOX_15-oxo-ETE 5280701 C04577 AA_LOX_5-HETE 5280733 C04805 AA_LOX_5-oxo-ETE 5283159 C14732 AA_LOX_6S-LXA4 42607306 AA_LOX_8-HETE 11976122 AA_LOX_9-HETE 14123398 AA_LOX_LTB4 5280492 C02165 AA_P450_11,12 DHET 5283146 C14774 AA_P450_11,12-EET 5283204 C14770 AA_P450_14,15 DHET 5283147 C14775 AA_P450_18-HETE 6442778 AA_P450_5,6 DHET 5283142 C14772 AA_P450_8,9 DHET 5283144 C14773 AA_P450_8,9-EET 5283203 C14769 METABOLITES_END #END