Extracellular Vesicles Maintain Blood-Brain Barrier Integrity by the Suppression of Caveolin-1/CD147/VEGFR2/MMP Pathway After Ischemic Stroke

References

• Popa-Wagner A, Petcu EB, Capitanescu B, Hermann DM, Radu E, Gresita A. Ageing as a risk factor for cerebral ischemia: underlying mechanisms and therapy in animal models and in the clinic. Mech Ageing Dev. 2020;190:111312. doi:10.1016/j.mad.2020.111312
   PubMed Web of Science ®Google Scholar
• Yousufuddin M, Young N. Aging and ischemic stroke. Aging. 2019;11(9):2542–2544. doi:10.18632/aging.101931
   PubMedGoogle Scholar
• Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics-2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139–e596. doi:10.1161/cir.0000000000000757
   PubMed Web of Science ®Google Scholar
• Yang Y, Rosenberg GA. Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke. 2011;42(11):3323–3328. doi:10.1161/strokeaha.110.608257
   PubMed Web of Science ®Google Scholar
• Jiang X, Andjelkovic AV, Zhu L, et al. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol. 2018;163–164:144–171. doi:10.1016/j.pneurobio.2017.10.001
   PubMed Web of Science ®Google Scholar
• Chamorro Á, Dirnagl U, Urra X, Planas AM. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurol. 2016;15(8):869–881. doi:10.1016/s1474-4422(16
   PubMed Web of Science ®Google Scholar
• Shi L, Rocha M, Leak RK, et al. A new era for stroke therapy: integrating neurovascular protection with optimal reperfusion. J Cereb Blood Flow Metab. 2018;38(12):2073–2091. doi:10.1177/0271678x18798162
   PubMed Web of Science ®Google Scholar
• Zivin JA. Acute stroke therapy with tissue plasminogen activator (tPA) since it was approved by the U.S. Food and Drug Administration (FDA). Ann Neurol. 2009;66(1):6–10. doi:10.1002/ana.21750
   PubMed Web of Science ®Google Scholar
• Reeves MJ, Arora S, Broderick JP, et al. Acute stroke care in the US: results from 4 pilot prototypes of the Paul Coverdell National Acute Stroke Registry. Stroke. 2005;36(6):1232–1240. doi:10.1161/01.STR.0000165902.18021.5b
   PubMed Web of Science ®Google Scholar
• Joo H, Wang G, George MG. Use of intravenous tissue plasminogen activator and hospital costs for patients with acute ischaemic stroke aged 18–64 years in the USA. Stroke Vasc Neurol. 2016;1(1):8–15. doi:10.1136/svn-2015-000002
   PubMedGoogle Scholar
• Kawabori M, Shichinohe H, Kuroda S, Houkin K. Clinical trials of stem cell therapy for cerebral ischemic stroke. Int J Mol Sci. 2020;21(19):7380. doi:10.3390/ijms21197380
   PubMed Web of Science ®Google Scholar
• Herberts CA, Kwa MS, Hermsen HP. Risk factors in the development of stem cell therapy. J Transl Med. 2011;9(1):29. doi:10.1186/1479-5876-9-29
   PubMedGoogle Scholar
• Eleuteri S, Fierabracci A. Insights into the secretome of mesenchymal stem cells and its potential applications. Int J Mol Sci. 2019;20(18). doi:10.3390/ijms20184597
   PubMed Web of Science ®Google Scholar
• Rahmani A, Saleki K, Javanmehr N, Khodaparast J, Saadat P, Nouri HR. Mesenchymal stem cell-derived extracellular vesicle-based therapies protect against coupled degeneration of the central nervous and vascular systems in stroke. Ageing Res Rev. 2020;62:101106. doi:10.1016/j.arr.2020.101106
   PubMed Web of Science ®Google Scholar
• van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–228. doi:10.1038/nrm.2017.125
   PubMed Web of Science ®Google Scholar
• Saint-Pol J, Gosselet F, Duban-Deweer S, Pottiez G, Karamanos Y. Targeting and crossing the blood-brain barrier with extracellular vesicles. Cells. 2020;9(4). doi:10.3390/cells9040851
   PubMed Web of Science ®Google Scholar
• Rufino-Ramos D, Albuquerque PR, Carmona V, Perfeito R, Nobre RJ, Pereira de Almeida L. Extracellular vesicles: novel promising delivery systems for therapy of brain diseases. J Control Release. 2017;262:247–258. doi:10.1016/j.jconrel.2017.07.001
   PubMed Web of Science ®Google Scholar
• Chen J, Chopp M. Exosome therapy for stroke. Stroke. 2018;49(5):1083–1090. doi:10.1161/STROKEAHA.117.018292
   PubMed Web of Science ®Google Scholar
• Li Y, Liu B, Chen Y, et al. Extracellular vesicle application as a novel therapeutic strategy for ischemic stroke. Transl Stroke Res. 2021. doi:10.1007/s12975-021-00915-3
   Web of Science ®Google Scholar
• Venkat P, Chen J, Chopp M. Exosome-mediated amplification of endogenous brain repair mechanisms and brain and systemic organ interaction in modulating neurological outcome after stroke. J Cereb Blood Flow Metab. 2018;38(12):2165–2178. doi:10.1177/0271678x18782789
   PubMed Web of Science ®Google Scholar
• Xin W, Qin Y, Lei P, Zhang J, Yang X, Wang Z. From cerebral ischemia towards myocardial, renal, and hepatic ischemia: exosomal miRNAs as a general concept of intercellular communication in ischemia-reperfusion injury. Mol Ther Nucleic Acids. 2022;29:900–922. doi:10.1016/j.omtn.2022.08.032
   PubMedGoogle Scholar
• Grass GD, Toole BP. How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity. Biosci Rep. 2015;36(1):e00283. doi:10.1042/BSR20150256
   PubMedGoogle Scholar
• Rempe RG, Hartz AMS, Bauer B. Matrix metalloproteinases in the brain and blood-brain barrier: versatile breakers and makers. J Cereb Blood Flow Metab. 2016;36(9):1481–1507. doi:10.1177/0271678x16655551
   PubMed Web of Science ®Google Scholar
• Chaturvedi M, Kaczmarek L. MMP-9 inhibition: a therapeutic strategy in ischemic stroke. Mol Neurobiol. 2014;49(1):563–573. doi:10.1007/s12035-013-8538-z
   PubMed Web of Science ®Google Scholar
• Patrizz A, Doran SJ, Chauhan A, et al. EMMPRIN/CD147 plays a detrimental role in clinical and experimental ischemic stroke. Aging. 2020;12(6):5121–5139. doi:10.18632/aging.102935
   PubMedGoogle Scholar
• Guo H, Li R, Zucker S, Toole BP. EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res. 2000;60(4):888–891.
   PubMed Web of Science ®Google Scholar
• Sun J, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res. 2001;61(5):2276–2281.
   PubMed Web of Science ®Google Scholar
• Liu Y, Qi L, Li Z, Yong VW, Xue M. Crosstalk between matrix metalloproteinases and their inducer EMMPRIN/CD147: a promising therapeutic target for intracerebral hemorrhage. Transl Stroke Res. 2023. doi:10.1007/s12975-023-01225-6
   Web of Science ®Google Scholar
• Liu S, Jin R, Xiao AY, Zhong W, Li G. Inhibition of CD147 improves oligodendrogenesis and promotes white matter integrity and functional recovery in mice after ischemic stroke. Brain Behav Immun. 2019;82:13–24. doi:10.1016/j.bbi.2019.07.027
   PubMed Web of Science ®Google Scholar
• Jin R, Xiao AY, Chen R, Granger DN, Li G. Inhibition of CD147 (Cluster of Differentiation 147) ameliorates acute ischemic stroke in mice by reducing thromboinflammation. Stroke. 2017;48(12):3356–3365. doi:10.1161/strokeaha.117.018839
   PubMed Web of Science ®Google Scholar
• Bougatef F, Quemener C, Kellouche S, et al. EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2alpha-mediated regulation of soluble VEGF isoforms and their receptor VEGFR-2. Blood. 2009;114(27):5547–5556. doi:10.1182/blood-2009-04-217380
   PubMed Web of Science ®Google Scholar
• Zong J, Li Y, Du D, Liu Y, Yin Y. CD147 induces up-regulation of vascular endothelial growth factor in U937-derived foam cells through PI3K/AKT pathway. Arch Biochem Biophys. 2016;609:31–38. doi:10.1016/j.abb.2016.09.001
   PubMed Web of Science ®Google Scholar
• Jickling GC, Liu D, Stamova B, et al. Hemorrhagic transformation after ischemic stroke in animals and humans. J Cereb Blood Flow Metab. 2014;34(2):185–199. doi:10.1038/jcbfm.2013.203
   PubMed Web of Science ®Google Scholar
• Won S, Lee JH, Wali B, Stein DG, Sayeed I. Progesterone attenuates hemorrhagic transformation after delayed tPA treatment in an experimental model of stroke in rats: involvement of the VEGF-MMP pathway. J Cereb Blood Flow Metab. 2014;34(1):72–80. doi:10.1038/jcbfm.2013.163
   PubMed Web of Science ®Google Scholar
• Huang Q, Zhong W, Hu Z, Tang X. A review of the role of cav-1 in neuropathology and neural recovery after ischemic stroke. J Neuroinflammation. 2018;15(1):348. doi:10.1186/s12974-018-1387-y
   PubMedGoogle Scholar
• Xie Y, Wang Y, Ding H, et al. Highly glycosylated CD147 promotes hemorrhagic transformation after rt-PA treatment in diabetes: a novel therapeutic target? J Neuroinflammation. 2019;16(1):72. doi:10.1186/s12974-019-1460-1
   PubMedGoogle Scholar
• Li Y, Liu B, Zhao T, et al. Comparative study of extracellular vesicles derived from mesenchymal stem cells and brain endothelial cells attenuating blood-brain barrier permeability via regulating Caveolin-1-dependent ZO-1 and Claudin-5 endocytosis in acute ischemic stroke. J Nanobiotechnol. 2023;21(1):70. doi:10.1186/s12951-023-01828-z
   PubMed Web of Science ®Google Scholar
• McMillin MA, Frampton GA, Seiwell AP, Patel NS, Jacobs AN, DeMorrow S. TGFβ1 exacerbates blood-brain barrier permeability in a mouse model of hepatic encephalopathy via upregulation of MMP9 and downregulation of claudin-5. Lab Invest. 2015;95(8):903–913. doi:10.1038/labinvest.2015.70
   PubMed Web of Science ®Google Scholar
• Lee YK, Uchida H, Smith H, Ito A, Sanchez T. The isolation and molecular characterization of cerebral microvessels. Nat Protoc. 2019;14(11):3059–3081. doi:10.1038/s41596-019-0212-0
   PubMed Web of Science ®Google Scholar
• Kim GS, Yang L, Zhang G, et al. Critical role of sphingosine-1-phosphate receptor-2 in the disruption of cerebrovascular integrity in experimental stroke. Nat Commun. 2015;6:7893. doi:10.1038/ncomms8893
   PubMed Web of Science ®Google Scholar
• Cao Y, Sun N, Yang JW, et al. Does acupuncture ameliorate motor impairment after stroke? An assessment using the CatWalk gait system. Neurochem Int. 2017;107:198–203. doi:10.1016/j.neuint.2016.10.014
   PubMed Web of Science ®Google Scholar
• Zhang L, Schallert T, Zhang ZG, et al. A test for detecting long-term sensorimotor dysfunction in the mouse after focal cerebral ischemia. J Neurosci Methods. 2002;117(2):207–214. doi:10.1016/s0165-0270(02)00114-0
   PubMed Web of Science ®Google Scholar
• Baek H, Pahk KJ, Kim MJ, Youn I, Kim H. Modulation of cerebellar cortical plasticity using low-intensity focused ultrasound for poststroke sensorimotor function recovery. Neurorehabil Neural Repair. 2018;32(9):777–787. doi:10.1177/1545968318790022
   PubMed Web of Science ®Google Scholar
• Liu J, Jin X, Liu KJ, Liu W. Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage. J Neurosci. 2012;32(9):3044–3057. doi:10.1523/jneurosci.6409-11.2012
   PubMed Web of Science ®Google Scholar
• Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977. doi:10.1126/science.aau6977
   PubMed Web of Science ®Google Scholar
• Boltze J, Arnold A, Walczak P, Jolkkonen J, Cui L, Wagner DC. The dark side of the force - constraints and complications of cell therapies for stroke. Front Neurol. 2015;6:155. doi:10.3389/fneur.2015.00155
   PubMed Web of Science ®Google Scholar
• Zhang ZG, Buller B, Chopp M. Exosomes - beyond stem cells for restorative therapy in stroke and neurological injury. Nat Rev Neurol. 2019;15(4):193–203. doi:10.1038/s41582-018-0126-4
   PubMed Web of Science ®Google Scholar
• Mahdavipour M, Hassanzadeh G, Seifali E, et al. Effects of neural stem cell-derived extracellular vesicles on neuronal protection and functional recovery in the rat model of middle cerebral artery occlusion. Cell Biochem Funct. 2019. doi:10.1002/cbf.3484
   PubMed Web of Science ®Google Scholar
• Xia Y, Ling X, Hu G, et al. Small extracellular vesicles secreted by human iPSC-derived MSC enhance angiogenesis through inhibiting STAT3-dependent autophagy in ischemic stroke. Stem Cell Res Ther. 2020;11(1):313. doi:10.1186/s13287-020-01834-0
   PubMed Web of Science ®Google Scholar
• Venkat P, Cui C, Chopp M, et al. MiR-126 mediates brain endothelial cell exosome treatment-induced neurorestorative effects after stroke in type 2 diabetes mellitus mice. Stroke. 2019;50(10):2865–2874. doi:10.1161/STROKEAHA.119.025371
   PubMed Web of Science ®Google Scholar
• Xu X, Zhang H, Li J, et al. Combination of EPC-EXs and NPC-EXs with miR-126 and miR-210 overexpression produces better therapeutic effects on ischemic stroke by protecting neurons through the Nox2/ROS and BDNF/TrkB pathways. Exp Neurol. 2022:114235. doi:10.1016/j.expneurol.2022.114235
   PubMed Web of Science ®Google Scholar
• Yang C, Hawkins KE, Dore S, Candelario-Jalil E. Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke. Am J Physiol Cell Physiol. 2019;316(2):C135–C153. doi:10.1152/ajpcell.00136.2018
   PubMed Web of Science ®Google Scholar
• Zhao BQ, Tejima E, Lo EH. Neurovascular proteases in brain injury, hemorrhage and remodeling after stroke. Stroke. 2007;38(2 Suppl):748–752. doi:10.1161/01.STR.0000253500.32979.d1
   PubMed Web of Science ®Google Scholar
• Cui J, Chen S, Zhang C, et al. Inhibition of MMP-9 by a selective gelatinase inhibitor protects neurovasculature from embolic focal cerebral ischemia. Mol Neurodegener. 2012;7:21. doi:10.1186/1750-1326-7-21
   PubMed Web of Science ®Google Scholar
• Tang W, Chang SB, Hemler ME. Links between CD147 function, glycosylation, and caveolin-1. Mol Biol Cell. 2004;15(9):4043–4050. doi:10.1091/mbc.e04-05-0402
   PubMed Web of Science ®Google Scholar
• Tang W, Hemler ME. Caveolin-1 regulates matrix metalloproteinases-1 induction and CD147/EMMPRIN cell surface clustering. J Biol Chem. 2004;279(12):11112–11118. doi:10.1074/jbc.M312947200
   PubMed Web of Science ®Google Scholar
• Madaro L, Antonangeli F, Favia A, et al. Knock down of caveolin-1 affects morphological and functional hallmarks of human endothelial cells. J Cell Biochem. 2013;114(8):1843–1851. doi:10.1002/jcb.24526
   PubMed Web of Science ®Google Scholar
• Jin X, Sun Y, Xu J, Liu W. Caveolin-1 mediates tissue plasminogen activator-induced MMP-9 up-regulation in cultured brain microvascular endothelial cells. J Neurochem. 2015;132(6):724–730. doi:10.1111/jnc.13065
   PubMed Web of Science ®Google Scholar
• 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 MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750. doi:10.1080/20013078.2018.1535750
   PubMed Web of Science ®Google Scholar