Imidazole propionate is a driver and therapeutic target in atherosclerosis

• 成果类型: Article
• 署名作者: Mastrangelo, Annalaura; Robles-Vera, Inaki; Mananes, Diego; Galan, Miguel; Femenia-Muina, Marcos; Redondo-Urzainqui, Ana; Barrero-Rodriguez, Rafael; Papaioannou, Eleftheria; Amores-Iniesta, Joaquin; Devesa, Ana; Lobo-Gonzalez, Manuel; Carreras, Alba; Beck, Katharina R.; Ivarsson, Sophie; Gummesson, Anders; Georgiopoulos, Georgios; Rodrigo-Tapias, Manuel; Martinez-Cano, Sarai; Fernandez-Lopez, Ivan; Nunez, Vanessa; Ferrarini, Alessia; Inohara, Naohiro; Stamatelopoulos, Kimon; Benguria, Alberto; Cibrian, Danay; Sanchez-Madrid, Francisco; Alonso-Herranz, Vanesa; Dopazo, Ana; Barbas, Coral; Vazquez, Jesus; Lopez, Juan Antonio; Gonzalez-Martin, Alicia; Nunez, Gabriel; Stellos, Konstantinos; Bergstrom, Goran; Backhed, Fredrik; Fuster, Valentin; Ibanez, Borja; Sancho, David
• 署名单位: Centro Nacional de Investigaciones Cardiovasculares (CNIC); Autonomous University of Madrid; Complutense University of Madrid; Autonomous University of Madrid; Consejo Superior de Investigaciones Cientificas (CSIC); Autonomous University of Madrid; Hospital Universitario La Paz; Icahn School of Medicine at Mount Sinai; CIBER - Centro de Investigacion Biomedica en Red; CIBERCV; University of Gothenburg; Sahlgrenska University Hospital; National & Kapodistrian University of Athens; University of London; King's College London; University of Patras; University of Michigan System; University of Michigan; Hospital de La Princesa; San Pablo CEU University; University of Michigan System; University of Michigan; University of Osaka; Ruprecht Karls University Heidelberg; German Centre for Cardiovascular Research; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Sahlgrenska University Hospital; Technical University of Denmark; Technical University of Denmark; Icahn School of Medicine at Mount Sinai
• 刊物名称: Nature
• ISSN/ISSBN: 0028-1759
• DOI: 10.1038/s41586-025-09263-w
• 发表日期: 2025-09-04
• 关键词: endothelial-cell function; subclinical atherosclerosis; macrophage mtor; gut; inflammation; progression; pesa; RISK

摘要

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 efficacy. Here, we observed that imidazole propionate (ImP), produced by microorganisms, is associated with the extent of atherosclerosis in mice and in two independent human cohorts. Furthermore, ImP administration to atherosclerosis-prone mice fed with chow diet was sufficient to induce atherosclerosis without altering the lipid profile, and was linked to activation of both systemic and local innate and adaptive immunity and inflammation. Specifically, we found that ImP caused atherosclerosis through the imidazoline-1 receptor (I1R, also known as nischarin) in myeloid cells. Blocking this ImP-I1R axis inhibited the development of atherosclerosis induced by ImP or high-cholesterol diet in mice. Identification of the strong association of ImP with active atherosclerosis and the contribution of the ImP-I1R axis to disease progression opens new avenues for improving the early diagnosis and personalized therapy of atherosclerosis.