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01-10-2020 | Stroke | Original Article

Implication of MicroRNA503 in Brain Endothelial Cell Function and Ischemic Stroke

Authors: Huiting Zhang, Qunwen Pan, Zi Xie, Yanyu Chen, Jinju Wang, Ji Bihl, Wangtao Zhong, Yanfang Chen, Bin Zhao, Xiaotang Ma

Published in: Translational Stroke Research | Issue 5/2020

Abstract

The role of miR-503 in brain endothelium and ischemic stroke (IS) remains unclear. We aimed to study the relationship between plasma miR-503 and the onset time, severity, subtypes, and von Willebrand Factor (vWF) level in IS patients and to investigate the roles and underlying mechanisms of miR-503 in middle cerebral artery occlusion (MCAO) mice and cultured cerebral vascular endothelial cells (ECs). In MCAO mice, the effects of plasma from acute severe IS patients (ASS) with or without miR-503 antagomir on brain and ECs damage were determined. In cultured human ECs, the effects of miR-503 overexpression or knockdown on the monolayer permeability, apoptosis, ROS, and NO generation were investigated. For mechanism study, the PI3K/Akt/eNOS pathway, cleaved caspase-3, and bcl-2 were analyzed. Results showed that plasma miR-503 was significantly increased in IS patients, especially in acute period and severe cases and subtypes of LAA and TACI, and was positively correlated with vWF. Logistic analysis indicated that miR-503 was an independent risk factor for IS, with the area under curve of 0.796 in ROC analysis. In MCAO mice, ASS pretreatment aggravated neurological injury, BBB damage, brain edema, CBF reduction, and decreased NO production while increased apoptosis and ROS generation in brain ECs, which were partly abolished by miR-503 antagomir. In cultured ECs, miR-503 overexpression and knockdown confirmed its effects on regulating monolayer permeability, cell apoptosis, NO, and ROS generation via PI3K/Akt/eNOS pathway or bcl-2 and cleaved caspase-3 proteins. These together indicate that miR-503 is a promising biomarker and novel therapeutic target for IS.

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Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health. 2013;1(5):e259–81. https://doi.org/10.1016/s2214-109x(13)70089-5.CrossRefPubMedPubMedCentral

Cojocarui IM, Cojocaru M, Sapira V, Socoliuc G, Hertea C, Paveliu SP. Changes in plasma matrix metalloproteinase-9 levels in patients with acute ischemic stroke. Rom J Intern Med = Revue roumaine de medecine interne. 2012;50(2):155–8.PubMed

Joseph K, Gill H, Timothy B, Mary GC, Giles D, Byrne CD, et al. IL-6 is a predictive biomarker for stroke associated infection and future mortality in the elderly after an ischemic stroke. Exp Gerontol. 2013;48(9):960–5. https://doi.org/10.1016/j.exger.2013.07.003.CrossRef

Bustamante A, Lã Pez-Cancio E, Pich S, Penalba A, Giralt D, Garciã-A-Berrocoso T, et al. Blood biomarkers for the early diagnosis of stroke: the stroke-chip study. Stroke. 2017;48(9):2419–25. https://doi.org/10.1161/strokeaha.117.017076.CrossRefPubMed

Liang TY, Lou JY. Increased expression of mir-34a-5p and clinical association in acute ischemic stroke patients and in a rat model. Med Sci Monit. 2016;22:2950–5.PubMedPubMedCentral

Chen Z, Wang K, Huang J, Zheng G, Lv Y, Luo N, et al. Upregulated serum MiR-146b serves as a biomarker for acute ischemic stroke. Cell Physiol Biochem. 2018;45(1):397–405. https://doi.org/10.1159/000486916.CrossRefPubMed

Yang G, Liu Z, Wang L, Chen X, Wang X, Dong Q, et al. MicroRNA-195 protection against focal cerebral ischemia by targeting CX3CR1. J Neurosurg. 2018:1–10. https://doi.org/10.3171/2018.5.jns173061.

Paone S, Baxter AA, Hulett MD, Poon IKH. Endothelial cell apoptosis and the role of endothelial cell-derived extracellular vesicles in the progression of atherosclerosis. Cell Mol Life Sci. 2019;76(6):1093–106.PubMed

Chen J, Ning R, Zacharek A, Cui C, Cui X, Yan T, et al. MiR-126 contributes to human umbilical cord blood cell-induced neurorestorative effects after stroke in type-2 diabetic mice. Stem Cells. 2016;34(1):102–13. https://doi.org/10.1002/stem.2193.CrossRefPubMedPubMedCentral

10.

Pan Q, Liao X, Liu H, Wang Y, Chen Y, Zhao B, et al. MicroRNA-125a-5p alleviates the deleterious effects of ox-LDL on multiple functions of human brain microvessel endothelial cells. Am J Phys Cell Phys. 2017;312(2):C119–c30. https://doi.org/10.1152/ajpcell.00296.2016.CrossRef

11.

Huang S, Lv Z, Guo Y, Li L, Zhang Y, Zhou L, et al. Identification of blood Let-7e-5p as a biomarker for ischemic stroke. PLoS One. 2016;11(10):e0163951. https://doi.org/10.1371/journal.pone.0163951.CrossRefPubMedPubMedCentral

12.

Jin F, Xin J. Circulating miR-126 and miR-130a levels correlate with lower disease risk, disease severity, and reduced inflammatory cytokine levels in acute ischemic stroke patients. Neurol Sci. 2018;39(10):1757–65. https://doi.org/10.1007/s10072-018-3499-7.CrossRefPubMed

13.

Caporali A, Meloni M, Nailor A, Mitić T, Shantikumar S, Riu F, et al. p75(NTR)-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte-endothelial crosstalk in diabetes after limb ischaemia. Nat Commun. 2015;6:8024. https://doi.org/10.1038/ncomms9024.CrossRefPubMedPubMedCentral

14.

Fei Y, Hou J, Xuan W, Zhang C, Meng X. The relationship of plasma miR-503 and coronary collateral circulation in patients with coronary artery disease. Life Sci. 2018;207:145–51. https://doi.org/10.1016/j.lfs.2018.06.001.CrossRefPubMed

15.

Caporali A, Meloni M, Vollenkle C, Bonci D, Sala-Newby GB, Addis R, et al. Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation. 2011;123(3):282–91. https://doi.org/10.1161/circulationaha.110.952325.CrossRefPubMed

16.

Hou LJ, Han JJ, Liu Y. Up-regulation of microRNA-503 by high glucose reduces the migration and proliferation but promotes the apoptosis of human umbilical vein endothelial cells by inhibiting the expression of insulin-like growth factor-1 receptor. Eur Rev Med Pharmacol Sci. 2018;22(11):3515–23. https://doi.org/10.26355/eurrev_201806_15178.CrossRefPubMed

17.

Yang C, Hawkins KE, Doré S, Candelario-Jalil E. Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke. Am J Physiol Cell Physiol. 2019;316(2):C135–C53. https://doi.org/10.1152/ajpcell.00136.2018.CrossRefPubMed

18.

Liu Y, Tang Q, Shao S, Chen Y, Chen W, Xu X. Lyophilized powder of catalpol and puerarin protected cerebral vessels from ischemia by its anti-apoptosis on endothelial cells. Int J Biol Sci. 2017;13(3):327–38. https://doi.org/10.7150/ijbs.17751.CrossRefPubMedPubMedCentral

19.

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):869–81. https://doi.org/10.1016/s1474-4422(16)00114-9.CrossRefPubMed

20.

Radak D, Katsiki N, Resanovic I, Jovanovic A, Sudar-Milovanovic E, Zafirovic S, et al. Apoptosis and acute brain ischemia in ischemic stroke. Curr Vasc Pharmacol. 2017;15(2):115–22.PubMed

21.

Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337–41. https://doi.org/10.1038/nature14432.CrossRefPubMedPubMedCentral

22.

Ramirez SH, Potula R, Fan S, Eidem T, Papugani A, Reichenbach N, et al. Methamphetamine disrupts blood-brain barrier function by induction of oxidative stress in brain endothelial cells. J Cereb Blood Flow Metab. 2009;29(12):1933–45. https://doi.org/10.1038/jcbfm.2009.112.CrossRefPubMedPubMedCentral

23.

Chu P, Han G, Ahsan A, Sun Z, Liu S, Zhang Z, et al. Phosphocreatine protects endothelial cells from Methylglyoxal induced oxidative stress and apoptosis via the regulation of PI3K/Akt/eNOS and NF-kappaB pathway. Vasc Pharmacol. 2017;91:26–35. https://doi.org/10.1016/j.vph.2016.08.012.CrossRef

24.

Man XF, Tan SW, Tang HN, Guo Y, Tang CY, Tang J, et al. MiR-503 inhibits adipogenesis by targeting bone morphogenetic protein receptor 1a. Am J Transl Res. 2016;8(6):2727–37.PubMedPubMedCentral

25.

Wu D, Lu P, Mi X, Miao J. Downregulation of miR-503 contributes to the development of drug resistance in ovarian cancer by targeting PI3K p85. Arch Gynecol Obstet. 2018;297(3):699–707. https://doi.org/10.1007/s00404-018-4649-0.CrossRefPubMed

26.

Li Q, Li C, Xi S, Li X, Ding L, Li M. The effects of photobiomodulation therapy on mouse pre-osteoblast cell line MC3T3-E1 proliferation and apoptosis via miR-503/Wnt3a pathway. Lasers Med Sci. 2019;34(3):607–14. https://doi.org/10.1007/s10103-018-2636-0.CrossRefPubMed

27.

Williams SR, Hsu F-C, Keene KL, Chen W-M, Dzhivhuho G, Rowles JL III, et al. Genetic drivers of von Willebrand factor levels in an ischemic stroke population and association with risk for recurrent stroke. Stroke. 2017;48(6):1444–50.PubMedPubMedCentral

28.

Xiang Y, Cheng J, Wang D, Hu X, Xie Y, Stitham J, et al. Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor. Blood. 2015;125(22):3377–87.PubMedPubMedCentral

29.

Woodhouse L, Scutt P, Krishnan K, Berge E, Gommans J, Ntaios G, et al. Effect of hyperacute administration (within 6 hours) of transdermal glyceryl trinitrate, a nitric oxide donor, on outcome after stroke: subgroup analysis of the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Stroke. 2015;46(11):3194–201.PubMed

30.

Song H, Zhou H, Qu Z, Hou J, Chen W, Cai W, et al. From analysis of ischemic mouse brain proteome to identification of human serum clusterin as a potential biomarker for severity of acute ischemic stroke. Transl Stroke Res. 2019;10(5):546–56. https://doi.org/10.1007/s12975-018-0675-2.CrossRefPubMed

31.

Peng G, Yuan Y, Wu S, He F, Hu Y, Luo B. MicroRNA let-7e is a potential circulating biomarker of acute stage ischemic stroke. Transl Stroke Res. 2015;6(6):437–45.PubMed

32.

Yaghi S, Herber C, Boehme AK, Andrews H, Willey JZ, Rostanski SK, et al. The association between diffusion MRI-defined infarct volume and NIHSS score in patients with minor acute stroke. J Neuroimaging. 2017;27(4):388–91. https://doi.org/10.1111/jon.12423.CrossRefPubMedPubMedCentral

33.

Foley LM, Hitchens TK, Barbe B, Zhang F, Ho C, Rao GR, et al. Quantitative temporal profiles of penumbra and infarction during permanent middle cerebral artery occlusion in rats. Transl Stroke Res. 2010;1(3):220–9.PubMedPubMedCentral

34.

Watanabe M, Aiso S, Hibi T, Watanabe N, Iwao Y, Yoshida T, et al. Alteration of T cell maturation and proliferation in the mouse thymus induced by serum factors from patients with ulcerative colitis. Clin Exp Immunol. 1987;68(3):596–604.PubMedPubMedCentral

35.

Li P, Shen M, Gao F, Wu J, Zhang J, Teng F, et al. An antagomir to microRNA-106b-5p ameliorates cerebral ischemia and reperfusion injury in rats via inhibiting apoptosis and oxidative stress. Mol Neurobiol. 2017;54(4):2901–21.PubMed

36.

Ansar S, Chatzikonstantinou E, Wistuba-Schier A, Mirau-Weber S, Fatar M, Hennerici MG, et al. Characterization of a new model of thromboembolic stroke in C57 black/6J mice. Transl Stroke Res. 2014;5(4):526–33.PubMed

37.

Lin HW, Saul L, Gresia VL, Neumann JT, Dave KR, Perez-Pinzon MA. Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia. Transl Stroke Res. 2014;5(1):109–17. https://doi.org/10.1007/s12975-013-0276-z.CrossRefPubMed

38.

Luh C, Feiler S, Frauenknecht K, Meyer S, Lubomirov LT, Neulen A, et al. The contractile apparatus is essential for the integrity of the blood-brain barrier after experimental subarachnoid hemorrhage. Transl Stroke Res. 2019;10(5):534–45.PubMed

39.

Pan Q, He C, Liu H, Liao X, Dai B, Chen Y, et al. Microvascular endothelial cells-derived microvesicles imply in ischemic stroke by modulating astrocyte and blood brain barrier function and cerebral blood flow. Mol Brain. 2016;9(1):63.PubMedPubMedCentral

40.

Ma X, Zhang H, Pan Q, Zhao Y, Chen J, Zhao B, et al. Hypoxia/aglycemia-induced endothelial barrier dysfunction and tight junction protein downregulation can be ameliorated by citicoline. PLoS One. 2013;8(12):e82604.PubMedPubMedCentral

41.

Paris F, Fuks Z, Kang A, Capodieci P, Juan G, Ehleiter D, et al. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science. 2001;293(5528):293–7.PubMed

42.

Chen J, Xiao X, Chen S, Zhang C, Chen J, Yi D, et al. Angiotensin-converting enzyme 2 priming enhances the function of endothelial progenitor cells and their therapeutic efficacy. Hypertension (Dallas, Tex : 1979). 2013;61(3):681–9. https://doi.org/10.1161/hypertensionaha.111.00202.CrossRef

43.

Liu Y, Pan Q, Zhao Y, He C, Bi K, Chen Y, et al. MicroRNA-155 regulates ROS production, NO generation, apoptosis and multiple functions of human brain microvessel endothelial cells under physiological and pathological conditions. J Cell Biochem. 2015;116(12):2870–81.PubMed

44.

Park L, Zhou P, Pitstick R, Capone C, Anrather J, Norris EH, et al. Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. Proc Natl Acad Sci. 2008;105(4):1347–52.PubMed

45.

Barwari T, Joshi A, Mayr M. MicroRNAs in cardiovascular disease. J Am Coll Cardiol. 2016;68(23):2577–84.PubMed

46.

He X-W, Shi Y-H, Zhao R, Liu Y-S, Li G-F, Hu Y, et al. Plasma levels of miR-125b-5p and miR-206 in acute ischemic stroke patients after recanalization treatment: a prospective observational study. J Stroke Cerebrovasc Dis. 2019;28(6):1654–61.PubMed

47.

Leung LY, Chan CPY, Leung YK, Jiang HL, Abrigo JM, Wang DF, et al. Comparison of miR-124-3p and miR-16 for early diagnosis of hemorrhagic and ischemic stroke. Clin Chim Acta. 2014;433:139–44.PubMed

48.

Llwyd O, Salinet AS, Panerai RB, Lam MY, Saeed NP, Brodie F, et al. Cerebral Haemodynamics following acute ischaemic stroke: effects of stroke severity and stroke subtype. Cerebrovasc Dis Extra. 2018;8:80–9.PubMedPubMedCentral

49.

Cherian P, Hankey GJ, Eikelboom JW, Thom J, Baker RI, McQuillan A, et al. Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes. Stroke. 2003;34(9):2132–7.PubMed

50.

Tu HT, Campbell BC, Christensen S, Desmond PM, De Silva DA, Parsons MW, et al. Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation. Int J Stroke. 2015;10(4):534–40. https://doi.org/10.1111/ijs.12007.CrossRefPubMed

51.

Tuttolomondo A, Casuccio A, Della Corte V, Maida C, Pecoraro R, Di Raimondo D, et al. Endothelial function and arterial stiffness indexes in subjects with acute ischemic stroke: relationship with TOAST subtype. Atherosclerosis. 2017;256:94–9. https://doi.org/10.1016/j.atherosclerosis.2016.10.044.CrossRefPubMed

52.

Adachi U, Tsutsumi Y, Iijima M, Mizuno S, Uchiyama S, Kitagawa K. Differences in endothelial function between ischemic stroke subtypes. J Stroke Cerebrovasc Dis. 2015;24(12):2781–6. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.08.009.CrossRefPubMed

53.

Jia L, Hao F, Wang W, Qu Y. Circulating miR-145 is associated with plasma high-sensitivity C-reactive protein in acute ischemic stroke patients. Cell Biochem Funct. 2015;33(5):314–9.PubMed

54.

Bai Y, Zhang Y, Han B, Yang L, Chen X, Huang R, et al. Circular RNA DLGAP4 ameliorates ischemic stroke outcomes by targeting miR-143 to regulate endothelial-mesenchymal transition associated with blood–brain barrier integrity. J Neurosci. 2018;38(1):32–50.PubMedPubMedCentral

55.

Béziaud T, Ru Chen X, El Shafey N, Fréchou M, Teng F, Palmier B, et al. Simvastatin in traumatic brain injury: effect on brain edema mechanisms. Crit Care Med. 2011;39(10):2300–7.PubMed

56.

Nakano T, Nishigami C, Irie K, Shigemori Y, Sano K, Yamashita Y, et al. Goreisan prevents brain edema after cerebral ischemic stroke by inhibiting aquaporin 4 upregulation in mice. J Stroke Cerebrovasc Dis. 2018;27(3):758–63. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.10.010.CrossRefPubMed

57.

Jin X, Liu J, Yang Y, Liu KJ, Yang Y, Liu W. Spatiotemporal evolution of blood brain barrier damage and tissue infarction within the first 3 h after ischemia onset. Neurobiol Dis. 2012;48(3):309–16.PubMed

58.

Bevers MB, Battey TWK, Ostwaldt AC, Jahan R, Saver JL, Kimberly WT, et al. Apparent diffusion coefficient signal intensity ratio predicts the effect of revascularization on ischemic cerebral edema. Cerebrovasc Dis. 2018;45:93–100. https://doi.org/10.1159/000487406.CrossRefPubMedPubMedCentral

59.

Jiang X, Andjelkovic AV, Zhu L, Yang T, Bennett MV, Chen J, et al. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol. 2018;163:144–71.PubMed

60.

Yeung PK, Lo AC, Leung JW, Chung SS, Chung SK. Targeted overexpression of endothelin-1 in astrocytes leads to more severe cytotoxic brain edema and higher mortality. J Cereb Blood Flow Metab. 2009;29(12):1891–902. https://doi.org/10.1038/jcbfm.2009.175.CrossRefPubMed

61.

Kaplan B, Brint S, Tanabe J, Jacewicz M, Wang X, Pulsinelli W. Temporal thresholds for neocortical infarction in rats subjected to reversible focal cerebral ischemia. Stroke. 1991;22(8):1032–9.PubMed

62.

Harston GW, Okell TW, Sheerin F, Schulz U, Mathieson P, Reckless I, et al. Quantification of serial cerebral blood flow in acute stroke using arterial spin labeling. Stroke. 2017;48(1):123–30.PubMed

63.

Davidson SM, Duchen MR. Endothelial mitochondria: contributing to vascular function and disease. Circ Res. 2007;100(8):1128–41.PubMed

64.

Sajja RK, Rahman S, Cucullo L. Drugs of abuse and blood-brain barrier endothelial dysfunction: a focus on the role of oxidative stress. J Cereb Blood Flow Metab. 2016;36(3):539–54.PubMed

65.

Vanhoutte PM, Zhao Y, Xu A, Leung SW. Thirty years of saying NO: sources, fate, actions, and misfortunes of the endothelium-derived vasodilator mediator. Circ Res. 2016;119(2):375–96.PubMed

66.

Debattisti V, Gerencser AA, Saotome M, Das S, Hajnoczky G. ROS control mitochondrial motility through p38 and the motor adaptor Miro/Trak. Cell Rep. 2017;21(6):1667–80. https://doi.org/10.1016/j.celrep.2017.10.060.CrossRefPubMedPubMedCentral

67.

Yuan T, Yang T, Chen H, Fu D, Hu Y, Wang J, et al. New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis. Redox Biol. 2018;20:247–60. https://doi.org/10.1016/j.redox.2018.09.025.CrossRefPubMedPubMedCentral

68.

Garrigue P, Giacomino L, Bucci C, Muzio V, Filannino MA, Sabatier F, et al. Single photon emission computed tomography imaging of cerebral blood flow, blood–brain barrier disruption, and apoptosis time course after focal cerebral ischemia in rats. Int J Stroke. 2016;11(1):117–26.PubMed

69.

Xia CF, Yin H, Borlongan CV, Chao L, Chao J. Kallikrein gene transfer protects against ischemic stroke by promoting glial cell migration and inhibiting apoptosis. Hypertension. 2004;43(2):452–9. https://doi.org/10.1161/01.HYP.0000110905.29389.e5.CrossRefPubMed

70.

Contestabile A. Role of nitric oxide in cerebellar development and function: focus on granule neurons. Cerebellum. 2012;11(1):50–61.PubMed

71.

Steinert JR, Kopp-Scheinpflug C, Baker C, Challiss RJ, Mistry R, Haustein MD, et al. Nitric oxide is a volume transmitter regulating postsynaptic excitability at a glutamatergic synapse. Neuron. 2008;60(4):642–56.PubMed

72.

Zhang R, Zhang L, Zhang Z, Wang Y, Lu M, LaPointe M, et al. A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats. Ann Neurol. 2001;50(5):602–11.PubMed

73.

Zhang C, Zhang Z, Zhao Q, Wang X, Ji H, Zhang Y. (S)-ZJM-289 preconditioning induces a late phase protection against nervous injury induced by transient cerebral ischemia and oxygen-glucose deprivation. Neurotox Res. 2014;26(1):16–31.PubMed

74.

Shapira S, Kadar T, Weissman BA. Dose-dependent effect of nitric oxide synthase inhibition following transient forebrain ischemia in gerbils. Brain Res. 1994;668(1–2):80–4.PubMed

75.

Sancesario G, Iannone M, Morello M, Nistico G, Bernardi G. Nitric oxide inhibition aggravates ischemic damage of hippocampal but not of NADPH neurons in gerbils. Stroke. 1994;25(2):436–43.PubMed

76.

Terpolilli NA, Kim S-W, Thal SC, Kuebler WM, Plesnila N. Inhaled nitric oxide reduces secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab. 2013;33(2):311–8.PubMed

77.

Gao F, Sabbineni H, Artham S, Somanath PR. Modulation of long-term endothelial-barrier integrity is conditional to the cross-talk between Akt and Src signaling. J Cell Physiol. 2017;232(10):2599–609. https://doi.org/10.1002/jcp.25791.CrossRefPubMedPubMedCentral

78.

Ohno S, Kuroda M. Exosome-mediated targeted delivery of miRNAs. Methods Mol Biol. 2016;1448:261–70. https://doi.org/10.1007/978-1-4939-3753-0_19.CrossRefPubMed

Title: Implication of MicroRNA503 in Brain Endothelial Cell Function and Ischemic Stroke
Authors: Huiting Zhang
Qunwen Pan
Zi Xie
Yanyu Chen
Jinju Wang
Ji Bihl
Wangtao Zhong
Yanfang Chen
Bin Zhao
Xiaotang Ma
Publication date: 01-10-2020
Publisher: Springer US
Keywords: Stroke
Biomarkers
Published in: Translational Stroke Research / Issue 5/2020
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-020-00794-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Implication of MicroRNA503 in Brain Endothelial Cell Function and Ischemic Stroke

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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