Summary of Study ST003932

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 PR002461. The data can be accessed directly via it's Project DOI: 10.21228/M8J25F This work is supported by NIH grant, U2C- DK119886.

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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.

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Study IDST003932
Study TitleImidazole propionate is a driver and therapeutic target in atherosclerosis (study 2)
Study SummaryAtherosclerosis (AT) is the primary underlying cause of cardiovascular diseases (CVDs). Current preventive strategies focus on the identification and treatment of traditional cardiovascular risk factors but often fail to detect individuals at risk of early vascular disease. Emerging research has identified novel contributors to the pathophysiology of atherosclerosis, emphasizing the need for alternative biomarkers and therapeutic targets to improve early diagnosis and treatment efficacy. In this project, we identified that the microbial metabolite imidazole propionate (ImP) is associated with atherosclerosis burden in mice. We further demonstrated that ImP is sensed by the host through the imidazoline-1 receptor (I1R), which can be pharmacologically blocked in vivo using AGN192403. To evaluate the therapeutic potential of AGN192403 in preventing ImP-induced atherosclerosis, we co-administered ImP and AGN192403 in the drinking water of chow-fed ApoE⁻/⁻ mice for 8 weeks. We then quantified ImP levels in the blood to determine whether AGN192403 affected systemic ImP concentrations. To assess the therapeutic efficacy of targeting the ImP/I1R axis, a second experiment was conducted in which ApoE⁻/⁻ mice were fed either a chow or high-cholesterol (HC) diet for 8 weeks, with AGN192403 treatment introduced during the final 4 weeks in the HC group. Blood ImP levels were again measured to evaluate the impact of AGN administration. In both experimental settings, AGN192403 treatment did not alter circulating ImP levels, suggesting that the observed effects were due to pathway inhibition rather than changes in ImP bioavailability. These findings support the potential of AGN192403 as a novel therapeutic strategy for atherosclerosis by targeting the ImP/I1R axis.
Institute
Centro Nacional de Investigaciones Cardiovasculares Carlos III
Last NameMastrangelo
First NameAnnalaura
AddressCalle de Melchor Fernández Almagro, 3 – 28029, Madrid (Spain)
Emailamastrangelo@cnic.es
Phone(+34)914531202
Submit Date2025-05-23
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2025-06-17
Release Version1
Annalaura Mastrangelo Annalaura Mastrangelo
https://dx.doi.org/10.21228/M8J25F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002461
Project DOI:doi: 10.21228/M8J25F
Project Title:Imidazole propionate is a driver and therapeutic target in atherosclerosis
Project Type:Original research
Project Summary:Atherosclerosis (AT) is the main underlying cause of cardiovascular diseases (CVDs). Its prevention is based on the detection and treatment of traditional cardiovascular risk factors (PMID:34120177) but often fails to identify individuals at risk for early vascular disease (PMID:25882487). Recent research has suggested new players in the pathophysiology of atherosclerosis (PMID: 33883728), highlighting the need for alternative disease biomarkers and therapeutic targets to improve early diagnosis and therapy efficacy. Here, we identified that microbially produced imidazole propionate (ImP) is associated with the extent of atherosclerosis in mice and in two independent human cohorts. Furthermore, ImP administration to atherosclerosis-prone mice fed chow diet was sufficient to induce atherosclerosis without altering the lipid profile, and it was linked to activation of both systemic and local innate and adaptive immunity and inflammation. Specifically, we found that ImP caused atherosclerosis through Imidazoline-1 receptor (I1R) expressed in myeloid cells. Blocking this ImP/I1R axis inhibited the development of atherosclerosis induced by ImP as well as by high cholesterol diet in mice. Identification of the strong association of ImP with active atherosclerosis, along with the discovery of the contribution of the ImP/I1R axis to disease progression opens new avenues for improving the early diagnosis and personalized therapy of atherosclerosis.
Institute:Centro Nacional de Investigaciones Cardiovasculares Carlos III
Last Name:Mastrangelo
First Name:Annalaura
Address:Calle de Melchor Fernández Almagro, 3 – 28029, Madrid (Spain)
Email:amastrangelo@cnic.es
Phone:(+34) 914531202

Subject:

Subject ID:SU004068
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Male and female

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Diet ImP AGN Sample source
SA446301IMP_PLUS3246.dC ImP AGN plasma
SA446302IMP_PLUS2427.dC ImP AGN plasma
SA446303IMP_PLUS2428.dC ImP AGN plasma
SA446304IMP_PLUS2429.dC ImP AGN plasma
SA446305IMP_PLUS2430.dC ImP AGN plasma
SA446306IMP_PLUS2431.dC ImP AGN plasma
SA446307IMP_PLUS2442.dC ImP AGN plasma
SA446308IMP_PLUS2444.dC ImP AGN plasma
SA446309IMP_PLUS2445.dC ImP AGN plasma
SA446310IMP_PLUS2446.dC ImP AGN plasma
SA446311IMP_PLUS3242.dC ImP AGN plasma
SA446312IMP_PLUS3243.dC ImP AGN plasma
SA446313IMP_PLUS3244.dC ImP AGN plasma
SA446314IMP_PLUS3245.dC ImP AGN plasma
SA446315IMP_PLUS3247.dC ImP AGN plasma
SA446316IMP_PLUS3248.dC ImP AGN plasma
SA446317IMP_PLUS3249.dC ImP AGN plasma
SA446318IMP2422.dC ImP No AGN plasma
SA446319IMP2423.dC ImP No AGN plasma
SA446320IMP2424.dC ImP No AGN plasma
SA446321IMP2425.dC ImP No AGN plasma
SA446322IMP2439.dC ImP No AGN plasma
SA446323IMP2440.dC ImP No AGN plasma
SA446324IMP2441.dC ImP No AGN plasma
SA446325IMP3252.dC ImP No AGN plasma
SA446326IMP3253.dC ImP No AGN plasma
SA446327IMP3254.dC ImP No AGN plasma
SA446328IMP3255.dC ImP No AGN plasma
SA446329IMP3256.dC ImP No AGN plasma
SA446330IIMP2437.dC ImP No AGN plasma
SA446331C2433.dC No ImP No AGN plasma
SA446332C2432.dC No ImP No AGN plasma
SA446333C3241.dC No ImP No AGN plasma
SA446334C2521.dC No ImP No AGN plasma
SA446335C3240.dC No ImP No AGN plasma
SA446336C3239.dC No ImP No AGN plasma
SA446337C3238.dC No ImP No AGN plasma
SA446338C3237.dC No ImP No AGN plasma
SA446339C2776.dC No ImP No AGN plasma
SA446340C2775.dC No ImP No AGN plasma
SA446341C2774.dC No ImP No AGN plasma
SA446342C2773.dC No ImP No AGN plasma
SA446343C2772.dC No ImP No AGN plasma
SA446344C2520.dC No ImP No AGN plasma
SA446345C2519.dC No ImP No AGN plasma
SA446346C2518.dC No ImP No AGN plasma
SA446347C2517.dC No ImP No AGN plasma
SA446348C2511.dC No ImP No AGN plasma
SA446349C2510.dC No ImP No AGN plasma
SA446350C2508.dC No ImP No AGN plasma
SA446351C2449.dC No ImP No AGN plasma
SA446352C2448.dC No ImP No AGN plasma
SA446353C2434.dC No ImP No AGN plasma
SA446354HC_PLUS2488.dHC No ImP AGN plasma
SA446355HC_PLUS2784.dHC No ImP AGN plasma
SA446356HC_PLUS2489.dHC No ImP AGN plasma
SA446357HC_PLUS2785.dHC No ImP AGN plasma
SA446358HC_PLUS2491.dHC No ImP AGN plasma
SA446359HC_PLUS2513.dHC No ImP AGN plasma
SA446360HC_PLUS2514.dHC No ImP AGN plasma
SA446361HC_PLUS2515.dHC No ImP AGN plasma
SA446362HC_PLUS2516.dHC No ImP AGN plasma
SA446363HC_PLUS2782.dHC No ImP AGN plasma
SA446364HC_PLUS2786.dHC No ImP AGN plasma
SA446365HC_PLUS2490.dHC No ImP AGN plasma
SA446366HC_PLUS2783.dHC No ImP AGN plasma
SA446367HC2503.dHC No ImP No AGN plasma
SA446368HC2492.dHC No ImP No AGN plasma
SA446369HC2493.dHC No ImP No AGN plasma
SA446370HC2494.dHC No ImP No AGN plasma
SA446371HC2495.dHC No ImP No AGN plasma
SA446372HC2777.dHC No ImP No AGN plasma
SA446373HC2504.dHC No ImP No AGN plasma
SA446374HC2505.dHC No ImP No AGN plasma
SA446375HC2506.dHC No ImP No AGN plasma
SA446376HC2778.dHC No ImP No AGN plasma
SA446377HC2779.dHC No ImP No AGN plasma
SA446378HC2780.dHC No ImP No AGN plasma
SA446379HC2781.dHC No ImP No AGN plasma
SA446380HC2496.dHC No ImP No AGN plasma
Showing results 1 to 80 of 80

Collection:

Collection ID:CO004061
Collection Summary:The data set corresponds to the quantification of ImP in plasma samples from two experiments. 1st experiment: ApoE-/- mice were fed chow diet for 8 weeks. ImP and AGN192403 (AGN) were administered or not to these mice in drinking water for the 8 weeks. 2nd experiment: ApoE-/- mice were fed a chow diet or high cholesterol (HC) diet for 8 weeks. At 4 weeks post-diet initiation, AGN192403 was administered (AGN) or not in the drinking water to mice fed HC diet until week 8, followed by sacrifice. After sacrifice, blood samples were collected and placed in EDTA-K3 tubes.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR004077
Treatment Summary:1st experimental design: ImP was administered (or not, CTR) in the presence of AGN192403 (AGN) or not (ImP) in drinking water to ApoE-/- mice fed chow diet for 8 weeks, followed by sacrifice. 2nd experiment:ApoE-/- mice were fed a chow diet or high cholesterol (HC) diet for 8 weeks. At 4 weeks post-diet initiation, AGN192403 was administered (AGN) or not in the drinking water to mice fed HC diet until week 8, followed by sacrifice. Details: High cholesterol diet (HC, 10% fat, 0.75% cholesterol, SSNIFF S9167-E011); Imidazole propionate (400μg/mouse/day, Biogen Cientifica BA-F-3185.0001); AGN192403 (30μg/mouse/day, Labclinics S.A B6583-10)

Sample Preparation:

Sampleprep ID:SP004074
Sampleprep Summary:Individual 1000PPM stock solutions of ImP (Sigma-Aldrich 77951) was prepared in ultrapure water and stored at -20ºC. Its dilution was then prepared in MeOH/EtOH (1:1, v/v) and stored at 4ºC. Blood samples were centrifuged at 2,750 x g at RT for 10 minutes to obtain plasma. 150 μL of MeOH/EtOH (1:1, v/v) were then added to 50 μL of plasma sample. Samples were vortex-mixed for 10 seconds and then centrifuged at 13,000 rpm for 20 minutes at 4ºC. 100 μL of supernatant were taken and transferred to LC vials for the analysis

Chromatography:

Chromatography ID:CH004903
Instrument Name:Agilent 1290 Infinity
Column Name:InfinityLab Poroshell 120 HILIC-Z column (150 x 2.1 mm, 2.7 μm)
Column Temperature:25ºC
Flow Gradient:The initial conditions at time 0 were 100 % B, decreasing to 70 % at 11.5 min. The gradient was then increased to 100 % B at time 12.0 min and held until the total run time of 15 min.
Flow Rate:0.50 mL/min
Solvent A:100% Water; 20 mM Ammonium formate (pH 3)
Solvent B:90% Acetonitrile/10% Water; 20 mM aqueous Ammonium formate (pH 3)
Chromatography Type:HILIC

Analysis:

Analysis ID:AN006457
Analysis Type:MS
Chromatography ID:CH004903
Num Factors:5
Num Metabolites:1
Rt Units:Minutes
Units:nMol
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