#METABOLOMICS WORKBENCH AnnalauraM_20250523_025322 DATATRACK_ID:5941 STUDY_ID:ST003932 ANALYSIS_ID:AN006457 PROJECT_ID:PR002461
VERSION             	1
CREATED_ON             	May 24, 2025, 3:12 am
#PROJECT
PR:PROJECT_TITLE                 	Imidazole propionate is a driver and therapeutic target in atherosclerosis
PR:PROJECT_TYPE                  	Original research
PR:PROJECT_SUMMARY               	Atherosclerosis (AT) is the main underlying cause of cardiovascular diseases
PR:PROJECT_SUMMARY               	(CVDs). Its prevention is based on the detection and treatment of traditional
PR:PROJECT_SUMMARY               	cardiovascular risk factors but often fails to identify individuals at risk for
PR:PROJECT_SUMMARY               	early vascular disease. Recent research has suggested new players in the
PR:PROJECT_SUMMARY               	pathophysiology of atherosclerosis, highlighting the need for alternative
PR:PROJECT_SUMMARY               	disease biomarkers and therapeutic targets to improve early diagnosis and
PR:PROJECT_SUMMARY               	therapy efficacy. Here, we identified that microbially produced imidazole
PR:PROJECT_SUMMARY               	propionate (ImP) is associated with the extent of atherosclerosis in mice and in
PR:PROJECT_SUMMARY               	two independent human cohorts. Furthermore, ImP administration to
PR:PROJECT_SUMMARY               	atherosclerosis-prone mice fed a chow diet was sufficient to induce
PR:PROJECT_SUMMARY               	atherosclerosis without altering the lipid profile, and it was linked to
PR:PROJECT_SUMMARY               	activation of both systemic and local innate and adaptive immunity and
PR:PROJECT_SUMMARY               	inflammation. Specifically, we found that ImP caused atherosclerosis through
PR:PROJECT_SUMMARY               	imidazoline-1 receptor (I1R) expressed in myeloid cells. Blocking this ImP/I1R
PR:PROJECT_SUMMARY               	axis inhibited the development of atherosclerosis induced by ImP as well as by a
PR:PROJECT_SUMMARY               	high-cholesterol diet in mice. Identification of the strong association of ImP
PR:PROJECT_SUMMARY               	with active atherosclerosis, along with the discovery of the contribution of the
PR:PROJECT_SUMMARY               	ImP/I1R axis to disease progression, opens new avenues for improving the early
PR:PROJECT_SUMMARY               	diagnosis and personalized therapy of atherosclerosis.
PR:INSTITUTE                     	Centro Nacional de Investigaciones Cardiovasculares Carlos III
PR:LAST_NAME                     	Mastrangelo
PR:FIRST_NAME                    	Annalaura
PR:ADDRESS                       	Calle de Melchor Fernández Almagro, 3 – 28029, Madrid (Spain)
PR:EMAIL                         	amastrangelo@cnic.es
PR:PHONE                         	+34914531202
#STUDY
ST:STUDY_TITLE                   	Imidazole propionate is a driver and therapeutic target in atherosclerosis
ST:STUDY_TITLE                   	(study 2)
ST:STUDY_SUMMARY                 	Atherosclerosis (AT) is the primary underlying cause of cardiovascular diseases
ST:STUDY_SUMMARY                 	(CVDs). Current preventive strategies focus on the identification and treatment
ST:STUDY_SUMMARY                 	of traditional cardiovascular risk factors but often fail to detect individuals
ST:STUDY_SUMMARY                 	at risk of early vascular disease. Emerging research has identified novel
ST:STUDY_SUMMARY                 	contributors to the pathophysiology of atherosclerosis, emphasizing the need for
ST:STUDY_SUMMARY                 	alternative biomarkers and therapeutic targets to improve early diagnosis and
ST:STUDY_SUMMARY                 	treatment efficacy. In this project, we identified that the microbial metabolite
ST:STUDY_SUMMARY                 	imidazole propionate (ImP) is associated with atherosclerosis burden in mice. We
ST:STUDY_SUMMARY                 	further demonstrated that ImP is sensed by the host through the imidazoline-1
ST:STUDY_SUMMARY                 	receptor (I1R), which can be pharmacologically blocked in vivo using AGN192403.
ST:STUDY_SUMMARY                 	To evaluate the therapeutic potential of AGN192403 in preventing ImP-induced
ST:STUDY_SUMMARY                 	atherosclerosis, we co-administered ImP and AGN192403 in the drinking water of
ST:STUDY_SUMMARY                 	chow-fed ApoE⁻/⁻ mice for 8 weeks. We then quantified ImP levels in the
ST:STUDY_SUMMARY                 	blood to determine whether AGN192403 affected systemic ImP concentrations. To
ST:STUDY_SUMMARY                 	assess the therapeutic efficacy of targeting the ImP/I1R axis, a second
ST:STUDY_SUMMARY                 	experiment was conducted in which ApoE⁻/⁻ mice were fed either a chow or
ST:STUDY_SUMMARY                 	high-cholesterol (HC) diet for 8 weeks, with AGN192403 treatment introduced
ST:STUDY_SUMMARY                 	during the final 4 weeks in the HC group. Blood ImP levels were again measured
ST:STUDY_SUMMARY                 	to evaluate the impact of AGN administration. In both experimental settings,
ST:STUDY_SUMMARY                 	AGN192403 treatment did not alter circulating ImP levels, suggesting that the
ST:STUDY_SUMMARY                 	observed effects were due to pathway inhibition rather than changes in ImP
ST:STUDY_SUMMARY                 	bioavailability. These findings support the potential of AGN192403 as a novel
ST:STUDY_SUMMARY                 	therapeutic strategy for atherosclerosis by targeting the ImP/I1R axis.
ST:INSTITUTE                     	Centro Nacional de Investigaciones Cardiovasculares Carlos III
ST:LAST_NAME                     	Mastrangelo
ST:FIRST_NAME                    	Annalaura
ST:ADDRESS                       	Calle de Melchor Fernández Almagro, 3 – 28029, Madrid (Spain)
ST:EMAIL                         	amastrangelo@cnic.es
ST:PHONE                         	(+34)914531202
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
SU:GENDER                        	Male and female
#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           	C2432	C2432.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2432.mzML
SUBJECT_SAMPLE_FACTORS           	C2433	C2433.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2433.mzML
SUBJECT_SAMPLE_FACTORS           	C2434	C2434.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2434.mzML
SUBJECT_SAMPLE_FACTORS           	C2448	C2448.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2448.mzML
SUBJECT_SAMPLE_FACTORS           	C2449	C2449.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2449.mzML
SUBJECT_SAMPLE_FACTORS           	C2508	C2508.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2508.mzML
SUBJECT_SAMPLE_FACTORS           	C2510	C2510.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2510.mzML
SUBJECT_SAMPLE_FACTORS           	C2511	C2511.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2511.mzML
SUBJECT_SAMPLE_FACTORS           	C2517	C2517.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2517.mzML
SUBJECT_SAMPLE_FACTORS           	C2518	C2518.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2518.mzML
SUBJECT_SAMPLE_FACTORS           	C2519	C2519.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2519.mzML
SUBJECT_SAMPLE_FACTORS           	C2520	C2520.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2520.mzML
SUBJECT_SAMPLE_FACTORS           	C2521	C2521.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2521.mzML
SUBJECT_SAMPLE_FACTORS           	C2772	C2772.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2772.mzML
SUBJECT_SAMPLE_FACTORS           	C2773	C2773.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2773.mzML
SUBJECT_SAMPLE_FACTORS           	C2774	C2774.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2774.mzML
SUBJECT_SAMPLE_FACTORS           	C2775	C2775.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2775.mzML
SUBJECT_SAMPLE_FACTORS           	C2776	C2776.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C2776.mzML
SUBJECT_SAMPLE_FACTORS           	C3237	C3237.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C3237.mzML
SUBJECT_SAMPLE_FACTORS           	C3238	C3238.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C3238.mzML
SUBJECT_SAMPLE_FACTORS           	C3239	C3239.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C3239.mzML
SUBJECT_SAMPLE_FACTORS           	C3240	C3240.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C3240.mzML
SUBJECT_SAMPLE_FACTORS           	C3241	C3241.d	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=C3241.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2488	HC_PLUS2488.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2488.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2489	HC_PLUS2489.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2489.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2490	HC_PLUS2490.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2490.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2491	HC_PLUS2491.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2491.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2513	HC_PLUS2513.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2513.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2514	HC_PLUS2514.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2514.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2515	HC_PLUS2515.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2515.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2516	HC_PLUS2516.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2516.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2782	HC_PLUS2782.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2782.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2783	HC_PLUS2783.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2783.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2784	HC_PLUS2784.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2784.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2785	HC_PLUS2785.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2785.mzML
SUBJECT_SAMPLE_FACTORS           	HC_PLUS2786	HC_PLUS2786.d	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC_PLUS2786.mzML
SUBJECT_SAMPLE_FACTORS           	HC2492	HC2492.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2492.mzML
SUBJECT_SAMPLE_FACTORS           	HC2493	HC2493.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2493.mzML
SUBJECT_SAMPLE_FACTORS           	HC2494	HC2494.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2494.mzML
SUBJECT_SAMPLE_FACTORS           	HC2495	HC2495.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2495.mzML
SUBJECT_SAMPLE_FACTORS           	HC2496	HC2496.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2496.mzML
SUBJECT_SAMPLE_FACTORS           	HC2503	HC2503.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2503.mzML
SUBJECT_SAMPLE_FACTORS           	HC2504	HC2504.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2504.mzML
SUBJECT_SAMPLE_FACTORS           	HC2505	HC2505.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2505.mzML
SUBJECT_SAMPLE_FACTORS           	HC2506	HC2506.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2506.mzML
SUBJECT_SAMPLE_FACTORS           	HC2777	HC2777.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2777.mzML
SUBJECT_SAMPLE_FACTORS           	HC2778	HC2778.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2778.mzML
SUBJECT_SAMPLE_FACTORS           	HC2779	HC2779.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2779.mzML
SUBJECT_SAMPLE_FACTORS           	HC2780	HC2780.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2780.mzML
SUBJECT_SAMPLE_FACTORS           	HC2781	HC2781.d	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=HC2781.mzML
SUBJECT_SAMPLE_FACTORS           	IIMP2437	IIMP2437.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IIMP2437.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS2427	IMP_PLUS2427.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS2427.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS2428	IMP_PLUS2428.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS2428.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS2429	IMP_PLUS2429.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS2429.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS2430	IMP_PLUS2430.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS2430.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS2431	IMP_PLUS2431.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS2431.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS2442	IMP_PLUS2442.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS2442.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS2444	IMP_PLUS2444.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS2444.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS2445	IMP_PLUS2445.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS2445.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS2446	IMP_PLUS2446.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS2446.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS3242	IMP_PLUS3242.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS3242.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS3243	IMP_PLUS3243.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS3243.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS3244	IMP_PLUS3244.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS3244.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS3245	IMP_PLUS3245.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS3245.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS3246	IMP_PLUS3246.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS3246.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS3247	IMP_PLUS3247.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS3247.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS3248	IMP_PLUS3248.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS3248.mzML
SUBJECT_SAMPLE_FACTORS           	IMP_PLUS3249	IMP_PLUS3249.d	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP_PLUS3249.mzML
SUBJECT_SAMPLE_FACTORS           	IMP2422	IMP2422.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP2422.mzML
SUBJECT_SAMPLE_FACTORS           	IMP2423	IMP2423.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP2423.mzML
SUBJECT_SAMPLE_FACTORS           	IMP2424	IMP2424.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP2424.mzML
SUBJECT_SAMPLE_FACTORS           	IMP2425	IMP2425.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP2425.mzML
SUBJECT_SAMPLE_FACTORS           	IMP2439	IMP2439.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP2439.mzML
SUBJECT_SAMPLE_FACTORS           	IMP2440	IMP2440.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP2440.mzML
SUBJECT_SAMPLE_FACTORS           	IMP2441	IMP2441.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP2441.mzML
SUBJECT_SAMPLE_FACTORS           	IMP3252	IMP3252.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP3252.mzML
SUBJECT_SAMPLE_FACTORS           	IMP3253	IMP3253.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP3253.mzML
SUBJECT_SAMPLE_FACTORS           	IMP3254	IMP3254.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP3254.mzML
SUBJECT_SAMPLE_FACTORS           	IMP3255	IMP3255.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP3255.mzML
SUBJECT_SAMPLE_FACTORS           	IMP3256	IMP3256.d	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	RAW_FILE_NAME(mzML file name)=IMP3256.mzML
#COLLECTION
CO:COLLECTION_SUMMARY            	Blood samples were collected at sacrifice from apoeko mice. for both
CO:COLLECTION_SUMMARY            	experiments.
CO:SAMPLE_TYPE                   	Blood (plasma)
#TREATMENT
TR:TREATMENT_SUMMARY             	The data set corresponds to the quantification of ImP in two experiments. 1st
TR:TREATMENT_SUMMARY             	experimental design: ImP was administered (or not, CTR) in the presence of
TR:TREATMENT_SUMMARY             	AGN192403 (AGN) or not (ImP) in drinking water to ApoE-/- mice fed chow diet for
TR:TREATMENT_SUMMARY             	8 weeks, followed by sacrifice. 2nd experiment:ApoE-/- mice were fed a chow diet
TR:TREATMENT_SUMMARY             	or high cholesterol (HC) diet for 8 weeks. At 4 weeks post-diet initiation,
TR:TREATMENT_SUMMARY             	AGN192403 was administered (AGN) or not in the drinking water to mice fed HC
TR:TREATMENT_SUMMARY             	diet until week 8, followed by sacrifice. Details: High cholesterol diet (HC,
TR:TREATMENT_SUMMARY             	10% fat, 0.75% cholesterol, SSNIFF S9167-E011); Imidazole propionate
TR:TREATMENT_SUMMARY             	(400μg/mouse/day, Biogen Cientifica BA-F-3185.0001); AGN192403
TR:TREATMENT_SUMMARY             	(30μg/mouse/day, Labclinics S.A B6583-10)
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	For the PESA cohort, individual 1000PPM stock solutions of ImP (Sigma-Aldrich
SP:SAMPLEPREP_SUMMARY            	77951), urocanic acid (Urocanic acid-1,2,3-13C3, Sigma-Aldrich: 709638) and
SP:SAMPLEPREP_SUMMARY            	histidine (L-Histidine-d3 hydrochloride monohydrate, Sigma-Aldrich:791318) were
SP:SAMPLEPREP_SUMMARY            	prepared in ultrapure water and stored at -20ºC. Their respective dilutions
SP:SAMPLEPREP_SUMMARY            	were then prepared in MeOH/EtOH (1:1, v/v) and stored at 4ºC
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Agilent 1290 Infinity
CH:COLUMN_NAME                   	InfinityLab Poroshell 120 HILIC-Z column (2.7 μm 150 x 2.1 mm, Agilent
CH:COLUMN_NAME                   	Technologies, Santa Clara, California)
CH:SOLVENT_A                     	20 mM ammonium formate in ultrapure water at pH 3
CH:SOLVENT_B                     	20 mM aqueous ammonium formate at pH 3 in ACN/H20 (9:1, v/v)
CH:FLOW_GRADIENT                 	The initial conditions at time 0 were 100 % B, decreasing to 70 % at 11.5 min.
CH:FLOW_GRADIENT                 	The gradient was then increased to 100 % B at time 12.0 min and held until the
CH:FLOW_GRADIENT                 	total run time of 15 min.
CH:FLOW_RATE                     	0.50 mL/min
CH:COLUMN_TEMPERATURE            	25
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Agilent 6460 QQQ
MS:INSTRUMENT_TYPE               	Triple quadrupole
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	. Raw signals for multiple reaction monitoring (MRM) transitions were checked,
MS:MS_COMMENTS                   	and peaks corresponding to all the targeted compounds were integrated by
MS:MS_COMMENTS                   	MassHunter Quantitative B.10.00 (Agilent Technologies). Multiple reaction
MS:MS_COMMENTS                   	monitoring transitions (collision energy, eV) were as follows: 141 > 123 (10)
MS:MS_COMMENTS                   	and 141 > 81 (26) for ImP. Quantification of ImP concentration was performed by
MS:MS_COMMENTS                   	generating a standard curve with known concentrations of this metabolite. The
MS:MS_COMMENTS                   	metabolite standard was analyzed alongside plasma samples using the LC-MS/MS
MS:MS_COMMENTS                   	method. Dilution of the plasma during sample preparation was also taken into
MS:MS_COMMENTS                   	account for quantification.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	nMol
MS_METABOLITE_DATA_START
Samples	C2432.d	C2433.d	C2434.d	C2448.d	C2449.d	C2508.d	C2510.d	C2511.d	C2518.d	C2519.d	C2520.d	C2521.d	C2772.d	C2773.d	C2774.d	C2775.d	C2776.d	C3237.d	C3238.d	C3239.d	C3240.d	C3241.d	HC_PLUS2488.d	HC_PLUS2489.d	HC_PLUS2490.d	HC_PLUS2491.d	HC_PLUS2513.d	HC_PLUS2514.d	HC_PLUS2515.d	HC_PLUS2516.d	HC_PLUS2782.d	HC_PLUS2783.d	HC_PLUS2784.d	HC_PLUS2785.d	HC_PLUS2786.d	HC2492.d	HC2493.d	HC2494.d	HC2495.d	HC2496.d	HC2503.d	HC2504.d	HC2505.d	HC2506.d	HC2777.d	HC2778.d	HC2779.d	HC2780.d	HC2781.d	IIMP2437.d	IMP_PLUS2427.d	IMP_PLUS2428.d	IMP_PLUS2429.d	IMP_PLUS2430.d	IMP_PLUS2431.d	IMP_PLUS2442.d	IMP_PLUS2444.d	IMP_PLUS2445.d	IMP_PLUS2446.d	IMP_PLUS3242.d	IMP_PLUS3243.d	IMP_PLUS3244.d	IMP_PLUS3245.d	IMP_PLUS3246.d	IMP_PLUS3247.d	IMP_PLUS3248.d	IMP_PLUS3249.d	IMP2422.d	IMP2423.d	IMP2424.d	IMP2425.d	IMP2439.d	IMP2440.d	IMP2441.d	IMP3252.d	IMP3253.d	IMP3254.d	IMP3255.d	IMP3256.d
Factors	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:HC | ImP:No ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma	Diet:C | ImP:ImP | AGN:No AGN | Sample source:plasma
Imidazole propionate	7.896695937	41.34698569	9.153313012	31.37972753	5.247804262	19.15627052	16.47881937	26.13192326	10.85260201	10.90972097	5.162125825	14.3725578	86.69943831	147.2526736	27.45993904	11.73080599	8.310808382	13.51577343	17.02858934	7.296946879	7.675359975	22.03363803	51.94969226	38.30540118	15.95046901	18.17810837	31.05843339	37.47717629	21.92653998	22.45489035	33.14327535	11.45949094	22.15501582	31.42256674	8.396486819	16.29318276	21.78374259	22.70478579	31.33688831	53.827478	49.15086332	24.09706039	30.8656569	20.66992291	17.94963254	15.2436219	22.77618448	14.25831988	57.79010571	83.76495184	7.625380887	48.82956918	76.8606978	48.06560312	119.2286849	58.5469319	21.43388897	13.05168189	40.8971739	399.4971318	169.2077731	240.4208339	217.9231043	132.4231641	93.00394329	168.6508632	165.0095297	13.42295512	28.0596881	18.7849973	35.09959966	113.0455577	28.18106588	86.09254938	339.9863175	240.1709385	195.8252075	317.8027422	223.0780903
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	retention index	quantified m/z	PubChem ID	KEGG ID
Imidazole propionate	7.42	141.0656	70630	C20522                      
METABOLITES_END
#END