Aortic aneurysm and dissection: complement and precision medicine in aortic disease.

IF 4.1 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Leonie Dreher, Malte B Kuehl, Ulrich O Wenzel, Dominik Kylies
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引用次数: 0

Abstract

Aortic disease encompasses life-threatening conditions such as aortic aneurysm and dissection, which are associated with high prevalence, morbidity, and mortality. The complement system, a key component of innate immunity, not only defends against pathogens but also maintains tissue homeostasis. Recent discoveries have expanded its role beyond immunity, linking complement dysregulation to numerous diseases and positioning it as a target for pharmacotherapy. Complement-based treatments for precision medicine are emerging, with several pharmaceuticals either already approved or under investigation. In aortic disease, complement activation and dysregulation have unveiled novel mechanisms and clinical implications. Human and experimental studies suggest that all three complement pathways contribute to disease pathophysiology. The complement system induces direct cellular damage via the membrane attack complex, as well as matrix-metalloproteinase (MMP)-associated tissue damage by promoting MMP-2 and MMP-9 expression. The anaphylatoxins C3a and C5a exacerbate disease by recruiting immune cells and triggering proinflammatory responses. Examples include neutrophil extracellular trap formation and cytokine release by polymorphonuclear neutrophils. These findings highlight the complement system as a promising novel diagnostic and therapeutic target in aortic disease with potential for individualized treatment. However, gaps remain, emphasizing the need for standardized multisite preclinical studies to improve reproducibility and translation. Biomarker studies must also be validated across diverse patient cohorts for clinical applicability. This review examines current knowledge regarding complement in aortic disease, aiming to evaluate its potential for innovative diagnostic and personalized treatment strategies.

主动脉疾病包括主动脉瘤和夹层等危及生命的疾病,这些疾病的发病率、发病率和死亡率都很高。补体系统是先天性免疫的关键组成部分,它不仅能抵御病原体,还能维持组织稳态。最近的研究发现,补体系统的作用已超越了免疫,将补体失调与多种疾病联系起来,并将其定位为药物治疗的靶点。以补体为基础的精准医学治疗正在兴起,有几种药物已经获得批准或正在研究中。在主动脉疾病中,补体激活和失调揭示了新的机制和临床意义。人体和实验研究表明,所有三种补体途径都有助于疾病的病理生理学。补体系统通过膜攻击复合体诱导直接的细胞损伤,并通过促进 MMP-2 和 MMP-9 的表达诱导基质金属蛋白酶(MMP)相关的组织损伤。C3a 和 C5a 类抗噬菌体毒素通过招募免疫细胞并引发促炎症反应而加重病情。这方面的例子包括中性粒细胞胞外陷阱的形成和多形核中性粒细胞释放细胞因子。这些研究结果突出表明,补体系统是主动脉疾病中一个很有前景的新型诊断和治疗靶点,具有个体化治疗的潜力。然而,差距依然存在,强调需要进行标准化的多点临床前研究,以提高可重复性和转化率。生物标志物研究也必须在不同的患者队列中进行验证,以确保临床适用性。本综述探讨了目前有关主动脉疾病中补体的知识,旨在评估补体在创新诊断和个性化治疗策略中的潜力。
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来源期刊
CiteScore
9.60
自引率
10.40%
发文量
202
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology-Heart and Circulatory Physiology publishes original investigations, reviews and perspectives on the physiology of the heart, vasculature, and lymphatics. These articles include experimental and theoretical studies of cardiovascular function at all levels of organization ranging from the intact and integrative animal and organ function to the cellular, subcellular, and molecular levels. The journal embraces new descriptions of these functions and their control systems, as well as their basis in biochemistry, biophysics, genetics, and cell biology. Preference is given to research that provides significant new mechanistic physiological insights that determine the performance of the normal and abnormal heart and circulation.
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