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微粒释放的药理学调节:动脉血栓血管疾病治疗的新策略。

Pharmacological modulation of microparticle release: new strategies for the management of atherothrombotic vascular disorders.

机构信息

University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, UK.

出版信息

Curr Pharm Des. 2012;18(6):840-9. doi: 10.2174/138161212799277789.

Abstract

Microparticles (MPs) are submicron vesicles (0.1-1 μm) shed from the membrane of platelets, monocytes, endothelial cells and other cell types. Abundant clinical evidence relates increased plasma levels of MPs with several cardiovascular and inflammatory diseases, being a topic of tremendous interest in recent years. MPs have been proposed as potential effectors in thrombosis, inflammation, vascular injury or angiogenesis. Although MPs were traditionally considered noxious actors, recent scientific advances revealed another layer of complexity with their diverse roles in the pathophysiology of thrombotic disorders. Therefore, whilst their impact on the evolution of the disease is indisputable, the milieu of factors regulating MP release is still an intriguing field. Since MPs have been shown to be involved in thrombosis and inflammatory diseases, modulation of their release might have important therapeutic applications and provide further insights into their (patho)physiological roles. In this regard, increasing clinical attention has been devoted to the effects of pharmacological agents on MP circulating levels and antigenic composition. This trend led to many recent studies with special focus on the pharmaceutical options to inhibit formation of procoagulant MPs. Thus, this review aims to summarize available clinical and in vitro literature on mechanisms triggering MP release and modulating their activity.

摘要

微粒(MPs)是从血小板、单核细胞、内皮细胞和其他细胞类型的膜上脱落的亚微米囊泡(0.1-1μm)。大量临床证据表明,血浆中 MPs 水平的升高与多种心血管和炎症性疾病有关,这是近年来的研究热点。MPs 被认为是潜在的效应物,在血栓形成、炎症、血管损伤或血管生成中发挥作用。虽然 MPs 传统上被认为是有害的,但最近的科学进展揭示了它们在血栓性疾病病理生理学中的复杂作用的另一层面。因此,尽管它们对疾病进展的影响是不可争议的,但调节 MP 释放的因素仍然是一个有趣的领域。由于 MPs 已被证明与血栓形成和炎症性疾病有关,因此调节其释放可能具有重要的治疗应用,并进一步深入了解它们的(病理)生理作用。在这方面,越来越多的临床关注集中在药物对 MP 循环水平和抗原组成的影响上。这种趋势导致了许多最近的研究,特别关注抑制促凝 MPs 形成的药物选择。因此,本综述旨在总结关于触发 MP 释放和调节其活性的机制的现有临床和体外文献。

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