Microvesicles in Atherosclerosis and Angiogenesis: From Bench to Bedside and Reverse.
Microvesicles in Atherosclerosis and Angiogenesis: From Bench to Bedside and Reverse.
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DOI：
10.3389/fcvm.2017.00077
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发表时间：
2017
影响因子：
3.6
通讯作者：
Padró T
中科院分区：
文献类型：
--
作者：
Badimon L;Suades R;Arderiu G;Peña E;Chiva-Blanch G;Padró T
动脉粥样硬化（AT）是一种进行性慢性疾病，涉及大中动脉脂质堆积、纤维化和炎症，是心血管疾病（CVD）的主要原因。 AT 是由血脂异常引起的，由先天性和适应性免疫反应介导。尽管降脂药物已被证明可以降低心血管事件 (CVE) 的风险，但 AT 相关的发病率和死亡率仍存在巨大负担。识别 CVE 风险增加的受试者以及发现新的治疗靶点以改进治疗策略仍未满足 CVD 的临床需求。微泡（MV），即活化细胞和凋亡细胞脱落的细胞外质膜小颗粒，与 CVD 的发展广泛相关。来自血管和常驻细胞的 MV 通过促进邻近细胞之间的生物信息交换，充当血流中的细胞效应器，并在疾病进展的所有阶段发挥关键作用。本文回顾了目前关于 MV 在 AT 和 CVD 中的作用的知识。人们的注意力集中在动脉粥样硬化血栓形成过程中MV介导的调节机制的新方面，从内皮功能障碍、血管壁炎症、氧化应激和细胞凋亡到凝血和血栓形成。还讨论了 MV 对血管重塑的贡献，特别强调 MV 对内皮细胞和平滑肌细胞之间串扰的影响，及其调节 AT 驱动的血管生成和新血管形成的活跃过程的作用。本综述还重点介绍了细胞源性 MV 在 CVD 中的潜在预后、诊断和治疗价值的最新发现和主要挑战。总之，MV 已成为动脉粥样硬化血栓形成中生物功能的新调节剂，并可能在心血管精准医学中发挥重要作用。然而，仍需要付出巨大努力才能将 MV 调节和功能的最新发现转化为临床。
Atherosclerosis (AT) is a progressive chronic disease involving lipid accumulation, fibrosis, and inflammation in medium and large-sized arteries, and it is the main cause of cardiovascular disease (CVD). AT is caused by dyslipidemia and mediated by both innate and adaptive immune responses. Despite lipid-lowering drugs have shown to decrease the risk of cardiovascular events (CVEs), there is a significant burden of AT-related morbidity and mortality. Identification of subjects at increased risk for CVE as well as discovery of novel therapeutic targets for improved treatment strategies are still unmet clinical needs in CVD. Microvesicles (MVs), small extracellular plasma membrane particles shed by activated and apoptotic cells have been widely linked to the development of CVD. MVs from vascular and resident cells by facilitating exchange of biological information between neighboring cells serve as cellular effectors in the bloodstream and play a key role in all stages of disease progression. This article reviews the current knowledge on the role of MVs in AT and CVD. Attention is focused on novel aspects of MV-mediated regulatory mechanisms from endothelial dysfunction, vascular wall inflammation, oxidative stress, and apoptosis to coagulation and thrombosis in the progression and development of atherothrombosis. MV contribution to vascular remodeling is also discussed, with a particular emphasis on the effect of MVs on the crosstalk between endothelial cells and smooth muscle cells, and their role regulating the active process of AT-driven angiogenesis and neovascularization. This review also highlights the latest findings and main challenges on the potential prognostic, diagnostic, and therapeutic value of cell-derived MVs in CVD. In summary, MVs have emerged as new regulators of biological functions in atherothrombosis and might be instrumental in cardiovascular precision medicine; however, significant efforts are still needed to translate into clinics the latest findings on MV regulation and function.