单克隆抗体在动脉粥样硬化治疗中的应用:现状与展望。

Alexander V Blagov, Elizaveta M Pleshko, Olga N Maltseva, Alikhan Z Asoyan, Alessio L Ravani, Alexander N Orekhov
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引用次数: 0

摘要

动脉粥样硬化仍然是世界范围内心血管疾病发病率和死亡率的主要原因,是冠心病和中风等主要疾病的潜在原因。动脉粥样硬化的发病机制与慢性炎症和脂质代谢失调密切相关,这一过程也与其他炎症性疾病如类风湿关节炎和牛皮癣有关。单克隆抗体(mab)已成为一种有前景的治疗策略,提供针对动脉粥样硬化关键分子驱动因素的靶向干预。本文综述了近年来针对低密度脂蛋白(LDL)和枯草素转化酶(PCSK9)等降脂途径以及肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和白细胞介素-17 (IL-17)等炎症介质的单克隆抗体的开发和临床应用进展。值得注意的是,抗pcsk9抗体如alirocumab和evolocumab在大规模临床试验中显示出LDL-C水平和心血管事件的显著降低。同样,针对炎症细胞因子的抗体已显示出降低血管炎症和相关风险的功效。本综述还讨论了治疗性单克隆抗体的优点和局限性,如其高特异性、潜在的不良免疫反应以及与组织渗透和成本相关的挑战。总的来说,单克隆抗体治疗在动脉粥样硬化治疗方面取得了重大进展,目前正在进行旨在优化疗效、安全性和可及性的研究。未来的发展方向包括开发新的单克隆抗体和联合治疗,以进一步改善动脉粥样硬化性疾病患者的心血管预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The use of monoclonal antibodies for the treatment of atherosclerosis: current status and prospects.

Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality worldwide, underlying major conditions such as coronary heart disease and stroke. The pathogenesis of atherosclerosis is tightly linked to chronic inflammation and dysregulated lipid metabolism, processes that are also implicated in other inflammatory diseases like rheumatoid arthritis and psoriasis. Monoclonal antibodies (mAbs) have emerged as a promising therapeutic strategy, offering targeted intervention against key molecular drivers of atherosclerosis. This review summarizes recent advances in the development and clinical application of mAbs targeting both lipid-lowering pathways-such as low-density lipoprotein (LDL) and proprotein convertase subtilisin/kexin type 9 (PCSK9)-and inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-17 (IL-17). Notably, anti-PCSK9 antibodies like alirocumab and evolocumab have demonstrated significant reductions in LDL-C levels and cardiovascular events in large-scale clinical trials. Similarly, antibodies targeting inflammatory cytokines have shown efficacy in reducing vascular inflammation and associated risks. The review also discusses the advantages and limitations of therapeutic mAbs, such as their high specificity, potential for adverse immune responses, and challenges related to tissue penetration and cost. Overall, monoclonal antibody therapy represents a significant advancement in the management of atherosclerosis, with ongoing research aimed at optimizing efficacy, safety, and accessibility. Future directions include the development of novel mAbs and combination therapies to further improve cardiovascular outcomes in patients with atherosclerotic disease.

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