丙酸咪唑是动脉粥样硬化的驱动因子和治疗靶点，这一成果由卡洛斯三世国家心血管研究中心（CNIC）David Sancho课题组经过不懈努力而取得。这一研究成果于2025年7月16日发表在国际顶尖学术期刊《自然》上。

课题组人员观察到微生物产生的咪唑丙酸酯（ImP）与小鼠和两个独立的人类队列中的动脉粥样硬化程度有关。

此外，给易发动脉粥样硬化的小鼠注射ImP足以诱导动脉粥样硬化，而不改变脂质谱，并且与全身和局部先天和适应性免疫和炎症的激活有关。具体来说，该研究团队发现ImP通过髓细胞中的咪唑啉-1受体（I1R，也称为nischarin）引导动脉粥样硬化。阻断这条ImP-I1R轴可抑制小鼠由ImP或高胆固醇饮食诱导的动脉粥样硬化的发展。发现ImP与活动性动脉粥样硬化的强相关性以及ImP-I1R轴对疾病进展的贡献，为改善动脉粥样硬化的早期诊断和个性化治疗开辟了新的途径。

据了解，动脉粥样硬化是心血管疾病的主要潜在病因。其预防是基于传统心血管危险因素的检测和治疗。然而，有早期血管疾病风险的个体往往不为人所知。最近的研究发现了动脉粥样硬化病理生理学中的新分子，强调需要替代疾病生物标志物和治疗靶点来提高早期诊断和治疗效果。

附：英文原文

Title: Imidazole propionate is a driver and therapeutic target in atherosclerosis

Author: Mastrangelo, Annalaura, Robles-Vera, Iaki, Maanes, Diego, Galn, Miguel, Femena-Muia, Marcos, Redondo-Urzainqui, Ana, Barrero-Rodrguez, Rafael, Papaioannou, Eleftheria, Amores-Iniesta, Joaqun, Devesa, Ana, Lobo-Gonzlez, Manuel, Carreras, Alba, Beck, Katharina R., Ivarsson, Sophie, Gummesson, Anders, Georgiopoulos, Georgios, Rodrigo-Tapias, Manuel, Martnez-Cano, Sarai, Fernndez-Lpez, Ivan, Nuez, Vanessa, Ferrarini, Alessia, Inohara, Naohiro, Stamatelopoulos, Kimon, Bengura, Alberto, Cibrian, Danay, Snchez-Madrid, Francisco, Alonso-Herranz, Vanesa, Dopazo, Ana, Barbas, Coral, Vzquez, Jess, Lpez, Juan Antonio, Gonzlez-Martn, Alicia, Nuez, Gabriel, Stellos, Konstantinos, Bergstrm, Gran, Bckhed, Fredrik, Fuster, Valentn, Ibaez, Borja, Sancho, David

Issue&Volume: 2025-07-16

Abstract: 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.

DOI: 10.1038/s41586-025-09263-w

Source: https://www.nature.com/articles/s41586-025-09263-w