切换至 "中华医学电子期刊资源库"

中华脑血管病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (05) : 451 -457. doi: 10.3877/cma.j.issn.1673-9248.2025.05.013

综述

星形胶质细胞衍生的细胞外囊泡在脑血管功能调控中的作用和机制研究进展
田婉君1, 马晓瑭2,()   
  1. 1 524023 广东 湛江,广东医科大学第一临床医学院
    2 524001 广东 湛江,广东医科大学附属医院神经病学研究所 广东省衰老相关心脑疾病重点实验室
  • 收稿日期:2025-01-23 出版日期:2025-10-01
  • 通信作者: 马晓瑭
  • 基金资助:
    国家自然科学基金(82170407); 广东省基础与应用基础研究基金(2020A1515010089,2021A1515010982)

Advances in the roles and mechanisms of astrocyte-derived extracellular vesicles in cerebrovascular function regulation

Wanjun Tian1, Xiaotang Ma2,()   

  1. 1 The First Clinical Medical College, Guangdong Medical University, Zhanjiang 524023, China
    2 Institute of Neurology, the Affiliated Hospital of Guangdong Medical University, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Zhanjiang 524001, China
  • Received:2025-01-23 Published:2025-10-01
  • Corresponding author: Xiaotang Ma
引用本文:

田婉君, 马晓瑭. 星形胶质细胞衍生的细胞外囊泡在脑血管功能调控中的作用和机制研究进展[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(05): 451-457.

Wanjun Tian, Xiaotang Ma. Advances in the roles and mechanisms of astrocyte-derived extracellular vesicles in cerebrovascular function regulation[J/OL]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2025, 19(05): 451-457.

脑血管功能障碍是脑血管疾病的重要病理基础,具有高致残率和病死率。星形胶质细胞衍生的细胞外囊泡(AC-EV)通过携带蛋白质、核酸等生物活性物质介导细胞间通讯,在生理及病理条件下对脑血管功能调控发挥重要作用。近年来,研究表明,AC-EV不仅参与脑血管功能的调控,其成分特征与功能改变、多组脑血管病(卒中、阿尔茨海默病和帕金森病等)的发生发展密切相关,已成为潜在的诊疗靶点。本文系统综述AC-EV调控脑血管功能的作用机制及其在疾病诊疗中的应用前景,旨在为脑血管功能障碍的精准干预策略提供理论依据。

Cerebrovascular dysfunction serves as a critical pathological basis for cerebrovascular diseases, characterized by high disability and mortality rates. Astrocyte-derived extracellular vesicle (AC-EV), which mediate intercellular communication by transporting bioactive substances such as proteins and nucleic acids, play a pivotal role in regulating cerebrovascular function under both physiological and pathological conditions. Recent studies have revealed that AC-EV not only participate in cerebrovascular homeostasis but also exhibit altered composition and function closely linked to the pathogenesis and progression of multiple cerebrovascular disorders, including stroke, Alzheimer's disease, and Parkinson's disease. As a result, they have emerged as promising diagnostic and therapeutic targets. This review systematically summarizes the mechanisms by which AC-EV regulate cerebrovascular function and explores their clinical prospects in disease diagnosis and treatment, aiming to provide a theoretical foundation for developing precise intervention strategies against cerebrovascular dysfunction.

图1 星形胶质细胞衍生的胞外囊泡(AC-EV)在脑血管功能调控中的作用机制图 注:VEGF为血管内皮生长因子;FGF-2为成纤维细胞生长因子-2;TGF-β1为转化生长因子β1;Shh为音猬因子;HMGB 1为高迁移率族蛋白1;VEGFR为血管内皮细胞表面受体;PTX3为五聚蛋白3;FABP7为脂肪酸结合蛋白7;IL-10为白细胞介素-10;TSP-2为血小板反应蛋白-2;HSP70为热休克蛋白70;Cav-1为小窝蛋白-1;MMP-9为基质金属蛋白酶-9
1
Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier [J]. Nat Rev Neurosci, 2006, 7(1): 41-53.
2
Sweeney MD, Zhao Z, Montagne A, et al. Blood-brain barrier: from physiology to disease and back [J]. Physiol Rev, 2019, 99(1): 21-78.
3
Khan H, Pan JJ, Li Y, et al. Native and bioengineered exosomes for ischemic stroke therapy [J]. Front Cell Dev Biol, 2021, 9: 619565.
4
Vanlandewijck M, He L, Mäe MA, et al. A molecular atlas of cell types and zonation in the brain vasculature [J]. Nature, 2018, 554(7693): 475-480.
5
Engelhardt B, Liebner S. Novel insights into the development and maintenance of the blood-brain barrier [J]. Cell Tissue Res, 2014, 355(3): 687-699.
6
Liu Z, Chopp M. Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke [J]. Prog Neurobiol, 2016, 144: 103-120.
7
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.
8
Xia X, Wang Y, Huang Y, et al. Exosomal miRNAs in central nervous system diseases: biomarkers, pathological mediators, protective factors and therapeutic agents [J]. Prog Neurobiol, 2019, 183: 101694.
9
Pan Q, He C, Liu H, et al. Microvascular endothelial cells-derived microvesicles imply in ischemic stroke by modulating astrocyte and blood brain barrier function and cerebral blood flow [J]. Mol Brain, 2016, 9(1): 63.
10
Fu J, Li L, Huo D, et al. Astrocyte-derived TGFβ1 facilitates blood-brain barrier function via non-canonical Hedgehog signaling in brain microvascular endothelial cells [J]. Brain Sci, 2021, 11(1): 77.
11
Fang J, Wang Z, Miao CY. Angiogenesis after ischemic stroke [J]. Acta Pharmacol Sin, 2023, 44(7): 1305-1321.
12
Söllvander S, Nikitidou E, Brolin R, et al. Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons [J]. Mol Neurodegener, 2016, 11(1): 38.
13
Holm MM, Kaiser J, Schwab ME. Extracellular vesicles: multimodal envoys in neural maintenance and repair [J]. Trends Neurosci, 2018, 41(6): 360-372.
14
Ogaki A, Ikegaya Y, Koyama R. Extracellular vesicles taken up by astrocytes [J]. Int J Mol Sci, 2021, 22(19): 10553.
15
D'Egidio F, Castelli V, D'Angelo M, et al. Brain incoming call from glia during neuroinflammation: roles of extracellular vesicles [J]. Neurobiol Dis, 2024, 201: 106663.
16
Upadhya R, Zingg W, Shetty S, et al. Astrocyte-derived extracellular vesicles: neuroreparative properties and role in the pathogenesis of neurodegenerative disorders [J]. J Control Release, 2020, 323: 225-239.
17
Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders [J]. Neuron, 2008, 57(2): 178-201.
18
Stamatovic SM, Johnson AM, Keep RF, et al. Junctional proteins of the blood-brain barrier: new insights into function and dysfunction [J]. Tissue Barriers, 2016, 4(1): e1154641.
19
Sweeney MD, Sagare AP, Zlokovic BV. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders [J]. Nat Rev Neurol, 2018, 14(3): 133-150.
20
Shindo A, Maki T, Mandeville ET, et al. Astrocyte-derived Pentraxin 3 supports blood-brain barrier integrity under acute phase of stroke [J]. Stroke, 2016, 47(4): 1094-1100.
21
Kriaučiūnaitė K, Kaušylė A, Pajarskienė J, et al. Immortalised hippocampal astrocytes from 3xTG-AD mice fail to support BBB integrity in vitro: role of extracellular vesicles in glial-endothelial communication [J]. Cell Mol Neurobiol, 2021, 41(3): 551-562.
22
Guérit S, Fidan E, Macas J, et al. Astrocyte-derived Wnt growth factors are required for endothelial blood-brain barrier maintenance [J]. Prog Neurobiol, 2021, 199: 101937.
23
Rui Q, Ni H, Lin X, et al. Astrocyte-derived fatty acid-binding protein 7 protects blood-brain barrier integrity through a caveolin-1/MMP signaling pathway following traumatic brain injury [J]. Exp Neurol, 2019, 322: 113044.
24
Michinaga S, Inoue A, Sonoda K, et al. Down-regulation of astrocytic sonic hedgehog by activation of endothelin ET(B) receptors: Involvement in traumatic brain injury-induced disruption of blood brain barrier in a mouse model [J]. Neurochem Int, 2021, 146: 105042.
25
Hou Y, Xie Y, Liu X, et al. Oxygen glucose deprivation-pretreated astrocyte-derived exosomes attenuates intracerebral hemorrhage (ICH)-induced BBB disruption through miR-27a-3p /ARHGAP25/Wnt/β-catenin axis [J]. Fluids Barriers CNS, 2024, 21(1): 8.
26
Prat A, Biernacki K, Wosik K, et al. Glial cell influence on the human blood-brain barrier [J]. Glia, 2001, 36(2): 145-155.
27
Williamson MR, Fuertes CJA, Dunn AK, et al. Reactive astrocytes facilitate vascular repair and remodeling after stroke [J]. Cell Rep, 2021, 35(4): 109048.
28
Proia P, Schiera G, Mineo M, et al. Astrocytes shed extracellular vesicles that contain fibroblast growth factor-2 and vascular endothelial growth factor [J]. Int J Mol Med, 2008, 21(1): 63-67.
29
Woodbury ME, Ikezu T. Fibroblast growth factor-2 signaling in neurogenesis and neurodegeneration [J]. J Neuroimmune Pharmacol, 2014, 9(2): 92-101.
30
Shim JW, Madsen JR. VEGF signaling in neurological disorders [J]. Int J Mol Sci, 2018, 19(1): 275.
31
Greenberg DA, Jin K. From angiogenesis to neuropathology [J]. Nature, 2005, 438(7070): 959-954.
32
Byrd N, Grabel L. Hedgehog signaling in murine vasculogenesis and angiogenesis [J]. Trends Cardiovasc Med, 2004, 14(8): 308-313.
33
Cabezas R, Avila-Rodriguez M, Vega-Vela NE, et al. Growth factors and astrocytes metabolism: possible roles for platelet derived growth factor [J]. Med Chem, 2016, 12(3): 204-210.
34
Del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia [J]. J Cereb Blood Flow Metab, 2003, 23(8): 879-894.
35
Kim JB, Lim CM, Yu YM, et al. Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain [J]. J Neurosci Res, 2008, 86(5): 1125-1131.
36
Hayakawa K, Pham LD, Katusic ZS, et al. Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery [J]. Proc Natl Acad Sci U S A, 2012, 109(19): 7505-7510.
37
Treutiger CJ, Mullins GE, Johansson AS, et al. High mobility group 1 B-box mediates activation of human endothelium [J]. J Intern Med, 2003, 254(4): 375-385.
38
Guo Z, Zhang L, Wu Z, et al. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model [J]. Cell Stem Cell, 2014, 14(2): 188-202.
39
Barthels D, Das H. Current advances in ischemic stroke research and therapies [J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(4): 165260.
40
Tian W, Sawyer A, Kocaoglu FB, et al. Astrocyte-derived thrombospondin-2 is critical for the repair of the blood-brain barrier [J]. Am J Pathol, 2011, 179(2): 860-868.
41
Tang B, Song M, Xie X, et al. Tumor necrosis factor-stimulated gene-6 (TSG-6) secreted by BMSCs regulates activated astrocytes by inhibiting NF-κB signaling pathway to ameliorate blood brain barrier damage after intracerebral hemorrhage [J]. Neurochem Res, 2021, 46(9): 2387-2402.
42
Zagrean AM, Hermann DM, Opris I, et al. Multicellular crosstalk between exosomes and the neurovascular unit after cerebral ischemia. Therapeutic implications [J]. Front Neurosci, 2018, 12: 811.
43
Cekanaviciute E, Fathali N, Doyle KP, et al. Astrocytic transforming growth factor-beta signaling reduces subacute neuroinflammation after stroke in mice [J]. Glia, 2014, 62(8): 1227-1240.
44
Choi YC, Dalakas MC. Expression of matrix metalloproteinases in the muscle of patients with inflammatory myopathies [J]. Neurology, 2000, 54(1): 65-71.
45
Kalela A, Pönniö M, Koivu TA, et al. Association of serum sialic acid and MMP-9 with lipids and inflammatory markers [J]. Eur J Clin Invest, 2000, 30(2): 99-104.
46
Jiang Y, He R, Shi Y, et al. Plasma exosomes protect against cerebral ischemia/reperfusion injury via exosomal HSP70 mediated suppression of ROS [J]. Life Sci, 2020, 256: 117987.
47
Wang Y, Li H, Sun H, et al. A2 reactive astrocyte-derived exosomes alleviate cerebral ischemia-reperfusion injury by delivering miR-628 [J]. J Cell Mol Med, 2024, 28(16): e70004.
48
Paravicini TM, Touyz RM. NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities [J]. Diabetes Care, 2008, 31 Suppl 2: S170-180.
49
Yang Y, Salayandia VM, Thompson JF, et al. Attenuation of acute stroke injury in rat brain by minocycline promotes blood-brain barrier remodeling and alternative microglia/macrophage activation during recovery [J]. J Neuroinflammation, 2015, 12: 26.
50
Shiroto T, Romero N, Sugiyama T, et al. Caveolin-1 is a critical determinant of autophagy, metabolic switching, and oxidative stress in vascular endothelium [J]. PLoS One, 2014, 9(2): e87871.
51
Zeng L, He X, Wang Y, et al. MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain [J]. Gene Ther, 2014, 21(1): 37-43.
52
Hall ED, Braughler JM. Central nervous system trauma and stroke. Ⅱ. Physiological and pharmacological evidence for involvement of oxygen radicals and lipid peroxidation [J]. Free Radic Biol Med, 1989, 6(3): 303-313.
53
Stewart R, Hope Hutson K, Nestorova GG. Therapeutic potential of astrocyte-derived extracellular vesicles in mitigating cytotoxicity and transcriptome changes in human brain endothelial cells [J]. Neuroscience, 2024, 560: 181-190.
54
Ha D, Yang N, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges [J]. Acta Pharm Sin B, 2016, 6(4): 287-296.
55
Oyarce K, Cepeda MY, Lagos R, et al. Neuroprotective and neurotoxic effects of glial-derived exosomes [J]. Front Cell Neurosci, 2022, 16: 920686.
56
Gordillo-Sampedro S, Antounians L, Wei W, et al. iPSC-derived healthy human astrocytes selectively load miRNAs targeting neuronal genes into extracellular vesicles [J]. Mol Cell Neurosci, 2024, 129: 103933.
[1] 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/OL]. 中华移植杂志(电子版), 2024, 18(03): 186-192.
[2] 于倩, 崔庆超, 范一卉, 姚瑶. 施旺细胞衍生的细胞外囊泡通过Wnt/β-catenin信号通路促进牙髓再生的机制研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(01): 1-11.
[3] 付爽, 刘语菲, 周洁, 周振宇, 王淑芳. 工程化小细胞外囊泡的制备方法和应用前景[J/OL]. 中华细胞与干细胞杂志(电子版), 2023, 13(06): 363-369.
[4] 程亚飞, 郭航. 中枢神经系统AQP4的调节机制研究进展[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(01): 48-54.
[5] 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/OL]. 中华重症医学电子杂志, 2024, 10(03): 265-270.
[6] 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/OL]. 中华重症医学电子杂志, 2024, 10(03): 253-257.
[7] 胡贤瑞, 马惠, 赵科洪, 陈港琳, 何竟. 基于倾向性评分匹配分析重症脑血管疾病患者早期康复物理治疗的临床效果[J/OL]. 中华脑科疾病与康复杂志(电子版), 2025, 15(04): 208-213.
[8] 张志勔, 李晓玲. 细胞外囊泡在多发性硬化疾病诊断中的新进展[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(06): 373-378.
[9] 张克, 杨占奇, 闫维, 张二明, 向平超. 持续气道正压通气对阻塞性睡眠呼吸暂停综合征患者发生心脑血管事件的影响[J/OL]. 中华临床医师杂志(电子版), 2024, 18(05): 433-440.
[10] 闵志群, 苏杭. 广州地区人群ALDH2多态性分布特征与心脑血管疾病的相关性研究[J/OL]. 中华临床实验室管理电子杂志, 2024, 12(02): 97-102.
[11] 王国峰, 吕舒, 肖金潭, 刘国力, 刘伯芹. 体重变异性与泛血管疾病关系的研究进展[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(02): 135-141.
[12] 乔红梅, 张京芬, 王宝军. 乳酸与乳酸化在缺血性卒中中的作用机制和研究进展[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(04): 274-279.
[13] 金小娟, 马晓瑭. 血管内皮细胞来源胞外囊泡在缺血性脑卒中作用的研究进展[J/OL]. 中华脑血管病杂志(电子版), 2024, 18(06): 621-629.
[14] 马高亭, 左颖婷, 雷少元, 莫然, 吴宜凡, 孟舒娟, 姜子颖, 吴月, 任怡, 王平平, 张倩, 马青峰, 宋海庆, 钟莲梅, 郝峻巍. 模仿目标临床试验在脑血管疾病领域的应用现状及展望[J/OL]. 中华脑血管病杂志(电子版), 2024, 18(03): 277-280.
[15] 贾诗琪, 荣冬梅, 叶晖, 温齐平, 唐芬, 李雪娇, 王伟. 颅内血管壁磁共振成像序列综述[J/OL]. 中华脑血管病杂志(电子版), 2024, 18(02): 185-189.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?