Daniel Elieh-Ali-Komi, Ilze Bot, Mónica Rodríguez-González, Marcus Maurer
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At a molecular level, MC-released proteases, especially cathepsin G, degrade low-density lipoproteins (LDL) and mediate LDL fusion and binding of LDL to proteoglycans (PGs). Through a complicated network of chemokines including CXCL1, MCs promote the recruitment of among others CXCR2<sup>+</sup> neutrophils, therefore, aggravating the inflammation of the plaque environment. Additionally, MCs produce extracellular traps which worsen inflammation and contribute to atherothrombosis. 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引用次数: 0
摘要
人们普遍认为肥大细胞(MCs)在过敏性疾病的发病机制中起着至关重要的作用,但随着时间的推移,人们发现肥大细胞在包括动脉粥样硬化在内的非过敏性疾病的病理生理学中也发挥着作用。MCs在动脉粥样硬化病理学中的作用得到了动脉粥样硬化斑块发展过程中MCs积累以及斑块内MCs数量与急性心血管事件相关性的支持。积聚在动脉粥样硬化斑块内的 MC 会释放出一系列介质,从而导致新生血管生成、斑块进展、不稳定、侵蚀、破裂和血栓形成。在分子水平上,MC 释放的蛋白酶(尤其是 cathepsin G)会降解低密度脂蛋白(LDL),并介导 LDL 融合以及 LDL 与蛋白聚糖(PGs)的结合。MCs 通过包括 CXCL1 在内的复杂趋化因子网络,促进 CXCR2+ 中性粒细胞等的招募,从而加剧斑块环境的炎症。此外,MCs 产生的细胞外捕获物会加重炎症并导致动脉粥样栓塞。总之,有证据表明,MCs 通过几种潜在的机制,积极地导致动脉粥样硬化斑块不稳定和急性心血管综合征,因此,研究干预措施以调节 MC 的活化是心血管医学的一个有趣的目标。
Cellular and Molecular Mechanisms of Mast Cells in Atherosclerotic Plaque Progression and Destabilization.
Mast cells (MCs) are commonly recognized for their crucial involvement in the pathogenesis of allergic diseases, but over time, it has come to light that they also play a role in the pathophysiology of non-allergic disorders including atherosclerosis. The involvement of MCs in the pathology of atherosclerosis is supported by their accumulation in atherosclerotic plaques upon their progression and the association of intraplaque MC numbers with acute cardiovascular events. MCs that accumulate within the atherosclerotic plaque release a cocktail of mediators through which they contribute to neovascularization, plaque progression, instability, erosion, rupture, and thrombosis. At a molecular level, MC-released proteases, especially cathepsin G, degrade low-density lipoproteins (LDL) and mediate LDL fusion and binding of LDL to proteoglycans (PGs). Through a complicated network of chemokines including CXCL1, MCs promote the recruitment of among others CXCR2+ neutrophils, therefore, aggravating the inflammation of the plaque environment. Additionally, MCs produce extracellular traps which worsen inflammation and contribute to atherothrombosis. Altogether, evidence suggests that MCs actively, via several underlying mechanisms, contribute to atherosclerotic plaque destabilization and acute cardiovascular syndromes, thus, making the study of interventions to modulate MC activation an interesting target for cardiovascular medicine.
期刊介绍:
Clinical Reviews in Allergy & Immunology is a scholarly journal that focuses on the advancement of clinical management in allergic and immunologic diseases. The journal publishes both scholarly reviews and experimental papers that address the current state of managing these diseases, placing new data into perspective. Each issue of the journal is dedicated to a specific theme of critical importance to allergists and immunologists, aiming to provide a comprehensive understanding of the subject matter for a wide readership.
The journal is particularly helpful in explaining how novel data impacts clinical management, along with advancements such as standardized protocols for allergy skin testing and challenge procedures, as well as improved understanding of cell biology. Ultimately, the journal aims to contribute to the improvement of care and management for patients with immune-mediated diseases.