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Open AccessReview

The Role of the NF-κB Signaling Pathway in Atherosclerotic Plaque Rupture and Targeted Therapeutic Strategies

by

Lihui Yin

^1,2,3,

Xuehua Wang

^1,2,3,

Ni Xiong

^1,2,3

,

Jinjie Xiong

^1,2,3,

Qianyi Liu

^1,2,3,

Han Li

^1,2,3,

Yanling Huang

^1,2,3

,

Jiaxi Lv

^1,2,3,

Yan Wang

^1,2,3,* and

Zhaohui Wang

^1,2,3,*

¹

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

²

Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

³

Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

^*

Authors to whom correspondence should be addressed.

Biomedicines 2026, 14(1), 201; https://doi.org/10.3390/biomedicines14010201 (registering DOI)

Submission received: 30 November 2025 / Revised: 29 December 2025 / Accepted: 8 January 2026 / Published: 16 January 2026

(This article belongs to the Special Issue Coronary Artery Disease: From Pathophysiology to Therapeutic Strategies)

Download Versions Notes

Abstract

Atherosclerosis (AS) is a disease characterized by chronic vascular wall inflammation and lipid deposition. Although lipid-lowering drugs such as statins have significantly reduced cardiovascular event rates, “residual inflammatory risk” remains a key factor driving disease progression and plaque rupture. As a central regulator of the inflammatory response, the nuclear factor-κappaB (NF-κB) signaling network comprises both canonical pro-inflammatory pathways and functionally more complex non-canonical pathways. Increasing evidence in recent years indicates that abnormal and sustained activation of the non-canonical NF-κB signaling pathway plays a pivotal role in driving plaque rupture. This review first elaborates on the shift in AS strategies from “lipid-lowering” to “anti-inflammatory” approaches, followed by an in-depth analysis of the molecular activation mechanisms of the NF-κB signaling pathway and its distinctiveness in the AS pathological process, along with its epigenetic regulation. It emphasizes how this pathway drives pathological angiogenesis and regulates vascular smooth muscle cell (VSMC) phenotypic switching and macrophage function, thereby forming a vicious cycle that amplifies inflammation and structural damage, ultimately leading to acute cardiovascular events. Finally, we systematically summarize current progress and challenges in drug development targeting the NF-κB pathway (e.g., targeting key kinases like NIK and IKKα), aiming to provide theoretical foundations and future directions for novel therapeutic strategies to stabilize coronary plaques and prevent acute coronary syndromes.

Keywords: NF-κB; inflammation; atherosclerosis; pathological angiogenesis; epigenetic regulation; NIK inhibitor

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MDPI and ACS Style

Yin, L.; Wang, X.; Xiong, N.; Xiong, J.; Liu, Q.; Li, H.; Huang, Y.; Lv, J.; Wang, Y.; Wang, Z. The Role of the NF-κB Signaling Pathway in Atherosclerotic Plaque Rupture and Targeted Therapeutic Strategies. Biomedicines 2026, 14, 201. https://doi.org/10.3390/biomedicines14010201

AMA Style

Yin L, Wang X, Xiong N, Xiong J, Liu Q, Li H, Huang Y, Lv J, Wang Y, Wang Z. The Role of the NF-κB Signaling Pathway in Atherosclerotic Plaque Rupture and Targeted Therapeutic Strategies. Biomedicines. 2026; 14(1):201. https://doi.org/10.3390/biomedicines14010201

Chicago/Turabian Style

Yin, Lihui, Xuehua Wang, Ni Xiong, Jinjie Xiong, Qianyi Liu, Han Li, Yanling Huang, Jiaxi Lv, Yan Wang, and Zhaohui Wang. 2026. "The Role of the NF-κB Signaling Pathway in Atherosclerotic Plaque Rupture and Targeted Therapeutic Strategies" Biomedicines 14, no. 1: 201. https://doi.org/10.3390/biomedicines14010201

APA Style

Yin, L., Wang, X., Xiong, N., Xiong, J., Liu, Q., Li, H., Huang, Y., Lv, J., Wang, Y., & Wang, Z. (2026). The Role of the NF-κB Signaling Pathway in Atherosclerotic Plaque Rupture and Targeted Therapeutic Strategies. Biomedicines, 14(1), 201. https://doi.org/10.3390/biomedicines14010201

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