Badimon Lina, Suades Rosa, Arderiu Gemma, Peña Esther, Chiva-Blanch Gemma, Padró Teresa
Cardiovascular Research Center (ICCC) and CiberCV, Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain.
Cardiovascular Research Chair, UAB, Barcelona, Spain.
Front Cardiovasc Med. 2017 Dec 18;4:77. doi: 10.3389/fcvm.2017.00077. eCollection 2017.
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.
动脉粥样硬化（AT）是一种进展性慢性疾病，涉及中大型动脉中的脂质蓄积、纤维化和炎症，是心血管疾病（CVD）的主要病因。AT由血脂异常引起，并由先天性和适应性免疫反应介导。尽管降脂药物已显示可降低心血管事件（CVE）的风险，但AT相关的发病和死亡负担仍然很重。识别CVE风险增加的受试者以及发现用于改进治疗策略的新治疗靶点仍是CVD未满足的临床需求。微泡（MVs）是由活化和凋亡细胞释放的小细胞外质膜颗粒，已被广泛认为与CVD的发展有关。来自血管和驻留细胞的MVs通过促进相邻细胞之间的生物信息交换，在血液中充当细胞效应器，并在疾病进展的各个阶段发挥关键作用。本文综述了关于MVs在AT和CVD中作用的当前知识。重点关注MV介导的调节机制的新方面，从内皮功能障碍、血管壁炎症、氧化应激和凋亡到动脉粥样硬化血栓形成进展和发展中的凝血和血栓形成。还讨论了MV对血管重塑的贡献，特别强调了MVs对内皮细胞和平滑肌细胞之间相互作用的影响，以及它们在调节AT驱动的血管生成和新生血管形成的活跃过程中的作用。本综述还强调了细胞衍生MVs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，MVs已成为动脉粥样硬化血栓形成中生物功能的新调节因子，可能有助于心血管精准医学；然而，仍需要做出重大努力，将关于MV调节和功能的最新发现转化为临床应用。
