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PERSPECTIVE ARTICLE

Immune memory in vascular disease: A trained immunity perspective on in-stent neoatherosclerosis

Heng Wang1,2 ,  Yaling Li3 ,  Keyi Fan4 ,  Qinqin Tian4 ,  Ziyan Wang5 ,  Taoran Zhao6 ,  Guoping Zheng1,2*
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1 Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
2 Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
3 Department of Vascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
4 Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
5 Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
6 Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi, China
Brain & Heart, 025520077 https://doi.org/10.36922/BH025520077
Received: 23 December 2025 | Revised: 20 January 2026 | Accepted: 2 February 2026 | Published online: 6 March 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

In-stent neoatherosclerosis (ISNA) has emerged as a major cause of late stent failure, yet its underlying mechanisms remain poorly understood. Clinical and imaging studies indicate that ISNA develops more rapidly and exhibits greater plaque vulnerability than native atherosclerosis, a phenomenon often described as “late catch-up.” Trained immunity (TRIM), a form of innate immune memory driven by metabolic and epigenetic reprogramming, has been increasingly implicated in atherosclerotic cardiovascular diseases but has not previously been linked to ISNA. In this article, we propose a novel hypothesis that ISNA is driven by TRIM in vascular resident cells and innate immune cells within the stented arterial microenvironment. Pre-existing atherosclerotic risk factors may establish central and peripheral TRIM, which can be reactivated by persistent proatherogenic conditions and stent-related stimuli. The rapid recall and amplified secondary responses characteristic of TRIM provide a plausible explanation for the accelerated progression and instability of ISNA lesions. This perspective highlights TRIM as a promising mechanistic framework and therapeutic target for the prevention and management of ISNA.

Keywords
In-stent neoatherosclerosis
Trained immunity
Innate immune memory
Atherosclerotic disease
Stent-related vascular injury
Immunometabolic reprogramming
Funding
This work was supported by the National Health and Medical Research Council of Australia (Grant No. 2027965).
Conflict of interest
The authors declare they have no competing interests.
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