切换至 "中华医学电子期刊资源库"

第五届中国出版政府奖音像电子网络出版物奖提名奖

中国科技核心期刊

中国科学引文数据库(CSCD)来源期刊

中华重症医学电子杂志 ›› 2024, Vol. 10 ›› Issue (03) : 265 -270. doi: 10.3877/cma.j.issn.2096-1537.2024.03.010

综述

细胞外囊泡在脓毒症血管内皮损伤作用中的研究进展
胡梓菡1, 彭菲1, 孙骎1, 杨毅1,()   
  1. 1. 210009 南京,江苏省重症医学重点实验室 东南大学附属中大医院重症医学科
  • 收稿日期:2023-06-29 出版日期:2024-08-28
  • 通信作者: 杨毅
  • 基金资助:
    国家自然科学基金项目(81971888,82202393,81901945); 科技部国家重点研发计划项目(2022YFC2504400); 江苏省重点研发计划项目(BE2022854); 江苏省"双创博士"人才计划项目(JSSCBO20220135)

Research progress of extracellular vesicles in vascular endothelial dysfunction in sepsis

Zihan Hu1, Fei Peng1, Qin Sun1, Yi Yang1,()   

  1. 1. Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
  • Received:2023-06-29 Published:2024-08-28
  • Corresponding author: Yi Yang
引用本文:

胡梓菡, 彭菲, 孙骎, 杨毅. 细胞外囊泡在脓毒症血管内皮损伤作用中的研究进展[J]. 中华重症医学电子杂志, 2024, 10(03): 265-270.

Zihan Hu, Fei Peng, Qin Sun, Yi Yang. Research progress of extracellular vesicles in vascular endothelial dysfunction in sepsis[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(03): 265-270.

脓毒症是感染时宿主反应失调导致的危及生命的器官功能障碍。血管内皮损伤是脓毒症的重要特征,抑制内皮损伤有助于改善脓毒症患者的器官功能和预后。细胞外囊泡(EV)作为细胞间通讯的重要载体,通过影响内皮屏障功能、黏附作用、凝血、血管生成、细胞死亡等过程在脓毒症血管内皮损伤中发挥了重要作用。本文对EV在脓毒症血管内皮损伤中的作用作一总结,以期进一步了解脓毒症的发病机制,并为脓毒症的治疗提供新的思路。

Sepsis is life-threatening organ dysfunction resulting from a dysregulated host response to infection. Vascular endothelial injury is an important feature of sepsis, and inhibiting endothelial injury can help to improve organ function and prognosis in patients with sepsis. As an important carrier of intercellular communication, extracellular vesicles play an important role in vascular endothelial injury in sepsis by affecting the endothelial barrier, leukocyte adhesion, coagulation, angiogenesis and cell death. This paper summarizes the role of extracellular vesicles in vascular endothelial injury in sepsis, in order to further understand the pathogenesis of sepsis and provide new ideas for sepsis treatment.

表1 EV对内皮的损伤和保护作用
图1 细胞外囊泡对脓毒症血管内皮的作用机制注:ATG7为自噬相关基因7;SERP1为应激相关内质网蛋白1;Src为SRC原癌基因,非受体酪氨酸激酶;VE-cadherin为VE-钙黏蛋白;IL-1β为白介素-1β;NF-κB为核因子κB;ICAM1为细胞间黏附分子1;TF为组织因子;Claudin5为紧密连接蛋白Claudin5;Alk为Alk受体酪氨酸激酶;CD为白细胞分化簇;siICAM1为小干扰细胞间黏附分子1;VCAM-1为血管黏附分子1;ROS为活性氧;SOD2为超氧化物歧化酶2;RPTOR为雷帕霉素蛋白激酶靶标;CREB为cAMP反应元件结合蛋白;ADSC为脂肪干细胞
1
Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study [J]. Lancet, 2020, 395(10219): 200-211.
2
Xie J, Wang H, Kang Y, et al. The epidemiology of sepsis in Chinese ICUs: a national cross-sectional survey [J]. Crit Care Med, 2020, 48(3): e209-e218.
3
Joffre J, Hellman J, Ince C, et al. Endothelial responses in sepsis [J]. Am J Respir Crit Care Med, 2020, 202(3): 361-370.
4
Cheng L, Hill AF. Therapeutically harnessing extracellular vesicles [J]. Nat Rev Drug Discov, 2022, 21(5): 379-399.
5
van Niel G, Carter DRF, Clayton A, et al. Challenges and directions in studying cell-cell communication by extracellular vesicles [J]. Nat Rev Mol Cell Biol, 2022, 23(5): 369-382.
6
Han L, Lam EWF, Sun Y. Extracellular vesicles in the tumor microenvironment: old stories, but new tales [J]. Mol Cancer, 2019, 18(1): 59.
7
Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes [J]. Science, 2020, 367(6478): eaau6977.
8
Zhang Y, Meng H, Ma R, et al. Circulating microparticles, blood cells, and endothelium induce procoagulant activity in sepsis through phosphatidylserine exposure [J]. Shock, 2016, 45(3): 299-307.
9
Mostefai HA, Meziani F, Mastronardi ML, et al. Circulating microparticles from patients with septic shock exert protective role in vascular function [J]. Am J Respir Crit Care Med, 2008, 178(11): 1148-1155.
10
Takei Y, Yamada M, Saito K, et al. Increase in circulating ACE-positive endothelial microparticles during acute lung injury [J]. Eur Respir J, 2019, 54(4): 1801188.
11
Chatterjee V, Yang X, Ma Y, et al. Endothelial microvesicles carrying Src-rich cargo impair adherens junction integrity and cytoskeleton homeostasis [J]. Cardiovasc Res, 2020, 116(8): 1525-1538.
12
Puhm F, Afonyushkin T, Resch U, et al. Mitochondria are a subset of extracellular vesicles released by activated monocytes and induce type Ⅰ IFN and TNF responses in endothelial cells [J]. Circ Res, 2019, 125(1): 43-52.
13
Zafrani L, Gerotziafas G, Byrnes C, et al. Calpastatin controls polymicrobial sepsis by limiting procoagulant microparticle release [J]. Am J Respir Crit Care Med, 2012, 185(7): 744-755.
14
Gao K, Jin J, Huang C, et al. Exosomes derived from septic mouse serum modulate immune responses via exosome-associated cytokines [J]. Front Immunol, 2019, 10: 1560.
15
Li G, Wang B, Ding X, et al. Plasma extracellular vesicle delivery of miR-210-3p by targeting ATG7 to promote sepsis-induced acute lung injury by regulating autophagy and activating inflammation [J]. Exp Mol Med, 2021, 53(7): 1180-1191.
16
Gao M, Yu T, Liu D, et al. Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1 [J]. Clin Sci (Lond), 2021, 135(2): 347-365.
17
Wang JG, Williams JC, Davis BK, et al. Monocytic microparticles activate endothelial cells in an IL-1β-dependent manner [J]. Blood, 2011, 118(8): 2366-2374.
18
Woei-A-Jin FJSH, van der Starre WE, Tesselaar MET, et al. Procoagulant tissue factor activity on microparticles is associated with disease severity and bacteremia in febrile urinary tract infections [J]. Thromb Res, 2014, 133(5): 799-803.
19
Di L, Zha C, Liu Y. Platelet-derived microparticles stimulated by anti-β2GPI/β2GPI complexes induce pyroptosis of endothelial cells in antiphospholipid syndrome [J]. Platelets, 2023, 34(1): 2156492.
20
Liang W, Chen J, Zheng H, et al. MiR-199a-5p-containing macrophage-derived extracellular vesicles inhibit SMARCA4 and alleviate atherosclerosis by reducing endothelial cell pyroptosis [J]. Cell Biol Toxicol, 2022, 39(3): 591-605.
21
Mitra S, Exline M, Habyarimana F, et al. Microparticulate Caspase 1 regulates Gasdermin D and pulmonary vascular endothelial cell injury [J]. Am J Respir Cell Mol Biol, 2018, 59(1): 56-64.
22
Qin X, Zhou Y, Jia C, et al. Caspase-1-mediated extracellular vesicles derived from pyroptotic alveolar macrophages promote inflammation in acute lung injury [J]. Int J Biol Sci, 2022, 18(4): 1521-1538.
23
Essandoh K, Yang L, Wang X, et al. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction [J]. Biochim Biophys Acta, 2015, 1852(11): 2362-2371.
24
Jiang L, Ni J, Shen G, et al. Upregulation of endothelial cell-derived exosomal microRNA-125b-5p protects from sepsis-induced acute lung injury by inhibiting topoisomerase Ⅱ alpha [J]. Inflamm Res, 2021, 70(2): 205-216.
25
Wei X, Yi X, Lv H, et al. MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy [J]. Cell Death Dis, 2020, 11(8): 657.
26
Li L, Huang L, Huang C, et al. The multiomics landscape of serum exosomes during the development of sepsis [J]. J Adv Res, 2022, 39: 203-223.
27
Zhou Y, Li P, Goodwin AJ, et al. Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury [J]. Crit Care, 2019, 23(1): 44.
28
Das K, Keshava S, Pendurthi UR, et al. Factor Ⅶa suppresses inflammation and barrier disruption through the release of EEVs and transfer of microRNA 10a [J]. Blood, 2022, 139(1): 118-133.
29
Shah T, Qin S, Vashi M, et al. Alk5/Runx1 signaling mediated by extracellular vesicles promotes vascular repair in acute respiratory distress syndrome [J]. Clin Transl Med, 2018, 7(1): 19.
30
Dutra Silva J, Su Y, Calfee CS, et al. Mesenchymal stromal cell extracellular vesicles rescue mitochondrial dysfunction and improve barrier integrity in clinically relevant models of ARDS [J]. Eur Respir J, 2021, 58(1): 2002978.
31
Zhou Y, Li P, Goodwin AJ, et al. Exosomes from endothelial progenitor cells improve the outcome of a murine model of sepsis [J]. Mol Ther, 2018, 26(5): 1375-1384.
32
Ju Z, Ma J, Wang C, Yu J, et al. Exosomes from iPSCs delivering siRNA attenuate intracellular adhesion molecule-1 expression and neutrophils adhesion in pulmonary microvascular endothelial cells [J]. Inflammation, 2017, 40(2): 486-496.
33
Delabranche X, Boisramé-Helms J, Asfar P, et al. Microparticles are new biomarkers of septic shock-induced disseminated intravascular coagulopathy [J]. Intensive Care Med, 2013, 39(10): 1695-1703.
34
Bao W, Xing H, Cao S, et al. Neutrophils restrain sepsis associated coagulopathy via extracellular vesicles carrying superoxide dismutase 2 in a murine model of lipopolysaccharide induced sepsis [J]. Nat Commun, 2022, 13(1): 4583.
35
Wu SC, Kuo PJ, Rau CS, et al. Increased angiogenesis by exosomes secreted by adipose-derived stem cells upon lipopolysaccharide stimulation [J]. Int J Mol Sci, 2021, 22(16): 8877.
36
Almeria C, Weiss R, Roy M, et al. Hypoxia conditioned mesenchymal stem cell-derived extracellular vesicles induce increased vascular tube formation in vitro [J]. Front Bioeng Biotechnol, 2019, 7: 292.
37
Soriano AO, Jy W, Chirinos JA, et al. Levels of endothelial and platelet microparticles and their interactions with leukocytes negatively correlate with organ dysfunction and predict mortality in severe sepsis [J]. Crit Care Med, 2005, 33(11): 2540-2546.
38
Choi H, Kim Y, Mirzaaghasi A, et al. Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality [J]. Sci Adv, 2020, 6(15): eaaz6980.
39
Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV 2014 guidelines [J]. J Extracell Vesicles, 2018, 7(1): 1535750.
40
Saharinen P, Eklund L, Alitalo K. Therapeutic targeting of the angiopoietin-TIE pathway [J]. Nat Rev Drug Discov, 2017, 16(9): 635-661.
[1] 樊恒, 孙敏, 朱建华. 红景天苷通过抑制PI3K/AKT/mTOR信号通路对大鼠脓毒症急性肾损伤的保护作用[J]. 中华危重症医学杂志(电子版), 2024, 17(03): 188-195.
[2] 贾亚娟, 蒙钰铭, 高志伟, 高素敏, 张劲松, 孙虹. 血小板与淋巴细胞比值、降钙素原和白细胞介素6联合检测对脓毒症患者预后价值的研究[J]. 中华危重症医学杂志(电子版), 2024, 17(02): 118-123.
[3] 冯芳, 陈宇, 杨静, 满珂, 蔡红燕, 李群. ω-3鱼油脂肪乳注射液在脓毒症患者中的应用:前瞻性、随机对照、先导试验[J]. 中华危重症医学杂志(电子版), 2024, 17(02): 136-139.
[4] 柯晴潆, 沈延飞, 许强宏, 蔡国龙. 预测脓毒性心肌病患者院内死亡风险列线图模型的构建及验证[J]. 中华危重症医学杂志(电子版), 2024, 17(01): 10-18.
[5] 吕军好, 林锦雯, 张心怡, 陈江华. 细胞外囊泡在肾移植诊断和治疗中的研究进展[J]. 中华移植杂志(电子版), 2024, 18(03): 186-192.
[6] 顾晓凌, 吴冠楠, 宋勇. 核因子E2相关因子2(Nrf2)与铁死亡在脓毒症相关急性肺损伤中的研究进展[J]. 中华肺部疾病杂志(电子版), 2024, 17(02): 324-328.
[7] 张宪超, 张实. 基于转录组数据分析识别脓毒症肺炎免疫表型[J]. 中华肺部疾病杂志(电子版), 2023, 16(06): 761-765.
[8] 尚明煦, 魏丽娟, 是若春. 血清CRP、BNP、PCT与脓毒症并发ALI程度的相关性[J]. 中华肺部疾病杂志(电子版), 2023, 16(06): 766-769.
[9] 李松栗, 黄蔚, 巢杰, 杨毅, 邱海波. 单核/巨噬细胞来源的细胞外囊泡在急性呼吸窘迫综合征中的研究进展[J]. 中华重症医学电子杂志, 2024, 10(03): 253-257.
[10] 李莉, 张丽娜, 钱招昕. 亚甲蓝——脓毒症休克的“魔法锦囊”?[J]. 中华重症医学电子杂志, 2024, 10(02): 136-142.
[11] 张引, 李国强. 亚甲蓝治疗脓毒症休克的研究进展[J]. 中华重症医学电子杂志, 2024, 10(02): 143-147.
[12] 庞明敏, 闫美辰, 刘光凤, 宫继斌, 许娜娜, 郑玥, 范少华, 王昊. 脓毒症液体复苏治疗策略的研究进展[J]. 中华重症医学电子杂志, 2024, 10(02): 189-195.
[13] 杨磊, 汪美华, 胡锦. 急性脑梗死去骨瓣术后合并碳青霉烯耐药肺炎克雷伯菌感染一例[J]. 中华重症医学电子杂志, 2024, 10(02): 200-204.
[14] 刘霞, 赵双平. TDM指导特重度烧伤脓毒症患者多黏菌素B的个体化治疗一例[J]. 中华重症医学电子杂志, 2024, 10(01): 85-89.
[15] 胡杰, 蔡国龙. 脓毒症合并低心功能指数患者PiCCO参数的聚类分析[J]. 中华重症医学电子杂志, 2024, 10(01): 25-30.
阅读次数
全文


摘要