Dataset Information

Host sensing of microbially produced imidazole propionate is a driver and therapeutic 1 target in atherosclerosis

ABSTRACT: Atherosclerosis is the main underlying cause of cardiovascular diseases (CVDs). Its prevention is based on the detection and treatment of traditional cardiovascular risk factors1 but often fails to identify individuals at risk for early vascular disease2. Recent research has suggested new players in the pathophysiology of atherosclerosis3, 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Macrophage

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Juan A Lopez

LAB HEAD: Juan A Lopez

PROVIDER: PXD063955 | Pride | 2025-09-15

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	JAL_LabDS_Ann2_PhoT1_Tp1_Fr1.raw	Raw
	JAL_LabDS_Ann2_PhoT1_Tp1_Fr2.raw	Raw
	JAL_LabDS_Ann2_PhoT1_Tp1_Fr3.raw	Raw
	JAL_LabDS_Ann2_PhoT1_Tp1_FrA.raw	Raw
	JAL_LabDS_Ann2_PhoT1_Tp1_FrA2.raw	Raw

Items per page:

1 - 5 of 43

Publications

Imidazole propionate is a driver and therapeutic target in atherosclerosis.

Mastrangelo Annalaura A Robles-Vera Iñaki I Mañanes Diego D Galán Miguel M Femenía-Muiña Marcos M Redondo-Urzainqui Ana A Barrero-Rodríguez Rafael R Papaioannou Eleftheria E Amores-Iniesta Joaquín J Devesa Ana A Lobo-González Manuel M Carreras Alba A Beck Katharina R KR Ivarsson Sophie S Gummesson Anders A Georgiopoulos Georgios G Rodrigo-Tapias Manuel M Martínez-Cano Sarai S Fernández-López Ivan I Nuñez Vanessa V Ferrarini Alessia A Inohara Naohiro N Stamatelopoulos Kimon K Benguría Alberto A Cibrian Danay D Sánchez-Madrid Francisco F Alonso-Herranz Vanesa V Dopazo Ana A Barbas Coral C Vázquez Jesús J López Juan Antonio JA González-Martín Alicia A Nuñez Gabriel G Stellos Konstantinos K Bergström Göran G Bäckhed Fredrik F Fuster Valentín V Ibañez Borja B Sancho David D

Nature 20250716 8079

Atherosclerosis is the main underlying cause of cardiovascular diseases. Its prevention is based on the detection and treatment of traditional cardiovascular risk factors1. However, individuals at risk for early vascular disease often remain unidentified2. Recent research has identified new molecules in the pathophysiology of atherosclerosis3, highlighting the need for alternative disease biomarkers and therapeutic targets to improve early diagnosis and therapy e ...[more]

PMID: 40670786

Similar Datasets

Project description:Atherosclerosis is the preliminary cause of coronary artery disease, one of the diseases that ac-count for the largest number of fatal mortalities. Physical activity is an effective strategy to restrain atherosclerosis from deterioration. Evidence indicated that the changes of proteomic profile is highly associated with the atherosclerosis development, but the mechanism behind the exercise for atherosclerosis amelioration has not yet been investigated from the proteomics perspective. Hence, the proteomic profiles could further elucidate the systematic effects of exercise interven-tion on ApoE knockout atherosclerotic model and high fat diet intervention. In current study, Apoeem1Narl/Narl mice were randomly allocated into a normal diet (ND), western diet (WD) and WD with 12 weeks exercise intervention (WD EX) groups. The plasm proteome between WD and WD EX demonstrate the significant difference, and ten major pathways, including cardiovascular disease (CVD)–hematological disease, cellular compromise–inflammatory response, protein synthesis, connective tissue disorders, cellular movement–immune cell tracking, inflammatory response, etc., were generated by the IPA analysis. The fourteen proteins (PROS, PROZ, C2, F5, C5, SERPINA 10, FGB, FGG, CFB, F12, CRP, CFHR1, HABP2, and PPIA) critically involved in CVD–hematological disease pathway showed significant difference among groups. The PROS, F5, C5, FGG, and CFB levels associated with thrombosis and atherosclerosis induced by WD were significantly decreased by exercise intervention in WD EX. Furthermore, the F5 and FGG were well-demonstrated the important roles for thrombosis of atherosclerotic pathogenesis but the complement factor C5 in the development of atherosclerosis is not fully understood. In current study, the exercise could significantly alleviate the significantly elevated C5 and inflammation induced by WD group in accordance to amelioration of atherosclerosis. Therefore, exercise could mitigate chemotaxis through the modulation of the C5 level and innate immunity, thereby alle-viating the pathogenesis of atherosclerosis in western-diet induced obese mice.