AUTHOR=Zhao Bing , Wan Jiayang , Zhou Huifen , Yang Jiehong , Wan Haitong 

TITLE=Trained immunity in atherosclerosis: plasticity, metabolic-vascular axis, and AI-driven precision remodeling

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1669796

DOI=10.3389/fimmu.2025.1669796

ISSN=1664-3224

ABSTRACT=Chronic inflammation linked to atherosclerosis is closely related to a trained immunoregulatory network. Traditional studies primarily focus on the pro-inflammatory memory of monocytes, they frequently neglect important aspects such as the cell’s plasticity, interactions between different organs, and the dynamic regulation of the metabolism-vascular axis. This review presents four novel frameworks, including the trained immunity plasticity spectrum model. It demonstrates how monocytes maintain a dynamic balance between pro-inflammatory, tolerogenic, and anti-inflammatory phenotypes, regulated by mTOR/AMPK signaling and competitive histone modifications. The trained immunity–metabolism–vascular axis shows that metabolic disorders can change the way immune memory is formed. They achieve this by modifying the vascular microenvironment through epigenetic changes, exosomes, and products of mitochondrial stress. The cross-organ trained immunity framework reveals how remote epigenetic communication between the bone marrow, gut, and liver influences the development of monocytes. Finally, dynamic immune reprogramming integrates CRISPR-based epigenetic editing, metabolism-focused interventions, and AI-driven multi-omics predictions. This approach signifies a major transition from simply alleviating symptoms to accurately reshaping immune memory. This review reinterprets the immunometabolic mechanisms of atherosclerosis. It also lays the foundation for personalized therapies enhanced by AI and explores new interdisciplinary research avenues.