Wang Kan, Yin Zheng, Zhang Yang, Wu Xianpeng, Fan Lin
Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China.
FASEB J. 2025 Sep 30;39(18):e71056. doi: 10.1096/fj.202502269R.
Atherosclerosis (AS) is a chronic, progressive inflammatory disorder characterized by the deposition of lipid-laden plaques, infiltration of immune cells, and remodeling of vascular structures within arterial walls. It remains the primary pathological driver of atherosclerotic coronary artery disease (ASCAD) and a major contributor to global mortality. While conventional lipid-lowering therapies, particularly statins, have significantly reduced the incidence of ASCAD by targeting hyperlipidemia, a considerable residual inflammatory risk continues to exist. This unresolved inflammation exacerbates plaque vulnerability, increases the likelihood of rupture, and precipitates thrombotic complications. Recent breakthroughs in understanding the complex inflammatory mechanisms underlying AS, including endothelial dysfunction, macrophage polarization, T-cell activation, and the release of pro-inflammatory cytokines, have revealed novel therapeutic targets. This mechanistic insight has spurred the development of innovative anti-inflammatory strategies, including monoclonal antibodies targeting specific cytokines (e.g., IL-1β, TNF-α), epigenetic modulators, and immune-based interventions. This review synthesizes the current understanding of the inflammatory pathogenesis of AS, evaluates the translational potential of emerging anti-inflammatory therapies, and discusses the challenges in optimizing the balance between efficacy and safety. By bridging discoveries in basic science with clinical applicability, this analysis aims to guide future research and foster therapeutic innovations in combating ASCAD.
动脉粥样硬化（AS）是一种慢性、进行性炎症性疾病，其特征是富含脂质的斑块沉积、免疫细胞浸润以及动脉壁内血管结构重塑。它仍然是动脉粥样硬化性冠状动脉疾病（ASCAD）的主要病理驱动因素，也是全球死亡率的主要促成因素。虽然传统的降脂疗法，特别是他汀类药物，通过针对高脂血症显著降低了ASCAD的发病率，但相当大的残余炎症风险仍然存在。这种未解决的炎症会加剧斑块易损性，增加破裂的可能性，并引发血栓并发症。最近在理解AS潜在的复杂炎症机制方面取得的突破，包括内皮功能障碍、巨噬细胞极化、T细胞活化以及促炎细胞因子的释放，揭示了新的治疗靶点。这种机制上的见解推动了创新抗炎策略的发展，包括靶向特定细胞因子（如IL-1β、TNF-α）的单克隆抗体、表观遗传调节剂和基于免疫的干预措施。本综述综合了目前对AS炎症发病机制的理解，评估了新兴抗炎疗法的转化潜力，并讨论了在优化疗效和安全性之间平衡方面的挑战。通过将基础科学的发现与临床适用性联系起来，本分析旨在指导未来的研究，并促进在对抗ASCAD方面的治疗创新。
