Summary of Study ST003928

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.

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.

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Study ID	ST003928
Study Title	Untargeted metabolomics links imidazole propionate and atherosclerosis
Study Summary	Atherosclerosis (AT) is the primary underlying cause of cardiovascular diseases (CVDs). Current preventive strategies rely on the detection and management of traditional cardiovascular risk factors (PMID: 34120177), yet they often fail to identify individuals at risk for early-stage vascular disease (PMID: 25882487). Emerging research has revealed novel contributors to the pathophysiology of atherosclerosis (PMID: 33883728), underscoring the need for alternative biomarkers and therapeutic targets to enhance early diagnosis and treatment efficacy. In this study, we identified the microbial metabolite imidazole propionate (ImP) as being strongly associated with atherosclerosis in both mice and two independent human cohorts. To uncover microbial metabolites that influence atherosclerosis progression, we employed an untargeted metabolomics approach in atherosclerosis-prone ApoE⁻/⁻ mice subjected to different diets, with or without antibiotic treatment to deplete the gut microbiota. This analysis revealed substantial remodeling of the plasma metabolome in response to dietary and microbiota changes. Among the differentially abundant metabolites, ImP emerged as a microbiota-dependent molecule closely linked to the extent 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	a.mastrangelo@cnic.es
Phone	(+34) 914531202
Submit Date	2025-05-21
Raw Data Available	Yes
Raw Data File Type(s)	mzML
Analysis Type Detail	LC-MS
Release Date	2025-06-21
Release Version	1

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:	SU004064
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090

Factors:

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

mb_sample_id	local_sample_id	Abx	Diet	Sample source
SA445792	H_P_7C	Abx	Chow	plasma
SA445793	H_P2_50C	Abx	Chow	plasma
SA445794	H_P2_49C	Abx	Chow	plasma
SA445795	H_P2_48C	Abx	Chow	plasma
SA445796	H_P2_47C	Abx	Chow	plasma
SA445797	H_P2_46C	Abx	Chow	plasma
SA445798	H_P_9C	Abx	Chow	plasma
SA445799	H_P_8C	Abx	Chow	plasma
SA445800	H_P_10C	Abx	Chow	plasma
SA445801	H_P_6C	Abx	Chow	plasma
SA445802	H_P_27C	Abx	HCHC	plasma
SA445803	H_P_26C	Abx	HCHC	plasma
SA445804	H_P2_61C	Abx	HCHC	plasma
SA445805	H_P2_68C	Abx	HCHC	plasma
SA445806	H_P2_67C	Abx	HCHC	plasma
SA445807	H_P2_66C	Abx	HCHC	plasma
SA445808	H_P_30C	Abx	HCHC	plasma
SA445809	H_P_29C	Abx	HCHC	plasma
SA445810	H_P2_70C	Abx	HCHC	plasma
SA445811	H_P_28C	Abx	HCHC	plasma
SA445812	H_P2_56C	Abx	HC	plasma
SA445813	H_P2_60C	Abx	HC	plasma
SA445814	H_P2_58C	Abx	HC	plasma
SA445815	H_P2_57C	Abx	HC	plasma
SA445816	H_2P_59C	Abx	HC	plasma
SA445817	H_P_20C	Abx	HC	plasma
SA445818	H_P_19C	Abx	HC	plasma
SA445819	H_P_18C	Abx	HC	plasma
SA445820	H_P_17C	Abx	HC	plasma
SA445821	H_P_16C	Abx	HC	plasma
SA445822	H_P_1C	No Abx	Chow	plasma
SA445823	H_P2_45C	No Abx	Chow	plasma
SA445824	H_P2_44C	No Abx	Chow	plasma
SA445825	H_P2_43C	No Abx	Chow	plasma
SA445826	H_P2_42C	No Abx	Chow	plasma
SA445827	H_P2_41C	No Abx	Chow	plasma
SA445828	H_P_5C	No Abx	Chow	plasma
SA445829	H_P_4C	No Abx	Chow	plasma
SA445830	H_P_3C	No Abx	Chow	plasma
SA445831	H_P_2C	No Abx	Chow	plasma
SA445832	H_P2_63C	No Abx	HCHC	plasma
SA445833	H_P_21C	No Abx	HCHC	plasma
SA445834	H_P2_65C	No Abx	HCHC	plasma
SA445835	H_P_22C	No Abx	HCHC	plasma
SA445836	H_P_23C	No Abx	HCHC	plasma
SA445837	H_P_24C	No Abx	HCHC	plasma
SA445838	H_P_25C	No Abx	HCHC	plasma
SA445839	H_P2_69C	No Abx	HCHC	plasma
SA445840	H_P2_62C	No Abx	HCHC	plasma
SA445841	H_P2_64C	No Abx	HCHC	plasma
SA445842	H_P_13C	No Abx	HC	plasma
SA445843	H_P_14C	No Abx	HC	plasma
SA445844	H_P_12C	No Abx	HC	plasma
SA445845	H_P2_55C	No Abx	HC	plasma
SA445846	H_P2_54C	No Abx	HC	plasma
SA445847	H_P2_53C	No Abx	HC	plasma
SA445848	H_P2_52C	No Abx	HC	plasma
SA445849	H_P2_51C	No Abx	HC	plasma
SA445850	H_P_15C	No Abx	HC	plasma
SA445851	H_P_11C	No Abx	HC	plasma

Showing results 1 to 60 of 60

Showing results 1 to 60 of 60

Collection:

Collection ID:	CO004057
Collection Summary:	ApoE-/- mice were fed different diets (chow, high cholesterol (HC), HC and high choline (HC/HC)) for 8 weeks. At 4 weeks post diet initiation, mice were treated or not with a cocktail of antibiotics (abx) in the drinking water. At sacrifice, aorta, heart, cecal content and plasma samples were collected in EDTA-K tubes and analyzed.
Sample Type:	Blood (plasma)

Treatment:

Treatment ID:	TR004073
Treatment Summary:	Plasma samples were prepared from whole blood collected in EDTA-K tubes. After gentle inversion to mix with the anticoagulant, samples were kept on ice and processed within 30 minutes to minimize metabolic alterations. Blood was centrifuged at 1,500–2,000 × g for 10–15 minutes at 4°C to separate plasma, which was carefully collected without disturbing the buffy coat and stored in aliquots at –80°C until analysis.

Treatment ID:

TR004073

Treatment Summary:

Plasma samples were prepared from whole blood collected in EDTA-K tubes. After gentle inversion to mix with the anticoagulant, samples were kept on ice and processed within 30 minutes to minimize metabolic alterations. Blood was centrifuged at 1,500–2,000 × g for 10–15 minutes at 4°C to separate plasma, which was carefully collected without disturbing the buffy coat and stored in aliquots at –80°C until analysis.

Sample Preparation:

Sampleprep ID:	SP004070
Sampleprep Summary:	Plasma samples (50 µL) were prepared as previously (PMID: 27163744). Briefly, proteins were removed by adding a cold (-20°C) mixture of Methanol:Ethanol (1:1, v/v) in a ratio 5:1 (solvent:sample) and by storing the samples on ice for 20 minutes. The samples were then centrifuged at 15700 g for 20 minutes at 4 °C and the supernatant was collected and placed in a LC vial for the subsequent analysis.

Sampleprep ID:

SP004070

Sampleprep Summary:

Plasma samples (50 µL) were prepared as previously (PMID: 27163744). Briefly, proteins were removed by adding a cold (-20°C) mixture of Methanol:Ethanol (1:1, v/v) in a ratio 5:1 (solvent:sample) and by storing the samples on ice for 20 minutes. The samples were then centrifuged at 15700 g for 20 minutes at 4 °C and the supernatant was collected and placed in a LC vial for the subsequent analysis.

Chromatography:

Chromatography ID:	CH004897
Instrument Name:	Thermo Dionex Ultimate 3000
Column Name:	Merck SeQuant ZIC-HILIC column (150 × 1 mm, 3.5 µm)
Column Temperature:	45℃
Flow Gradient:	gradient started from 90 % to 25 % of B in 15 min, keeping constant for 3 min and returned to starting conditions in 0.1 min, finally by keeping the re-equilibration at 90 % of B for 11.9 min.
Flow Rate:	180 µL/min
Solvent A:	100% Water; 0.01% formic acid
Solvent B:	100% Acetonitrile; 0.01% formic acid
Chromatography Type:	HILIC

Analysis:

Analysis ID:	AN006451
Analysis Type:	MS
Chromatography ID:	CH004897
Has Mz:	1
Has Rt:	1
Rt Units:	Minutes
Results File:	ST003928_AN006451_Results.txt
Units:	Relative abundance