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Published in: Journal of Thrombosis and Thrombolysis 2/2023

Open Access 08-06-2023 | Stroke

The potential role of micro-RNA 125b-5p level in predicting outcome from thrombolytic therapy in patients with acute ischemic stroke

Authors: Sara Mostafa, Hatem Al Masry, Mona Hussein, Rehab M. Abd Elkareem, Mohammed M. Masoud

Published in: Journal of Thrombosis and Thrombolysis | Issue 2/2023

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Abstract

Several studies highlighted a significant role of specific miRNA as diagnostic and prognostic biomarkers for acute ischemic stroke. The aim of this work was to study micro-RNA 125b-5p level in patients with acute ischemic stroke in relation to stroke etiology, risk factors, severity and outcome. This case–control study was conducted on 40 patients with acute ischemic stroke eligible for receiving rt-PA and 40 age and sex matched healthy controls, Patients were submitted to neurological and radiological assessment. Functional outcome after 3 months was assessed using the modified Rankin Scale (mRS). Plasma micro-RNA 125b-5p levels were measured for both patients and control groups by quantitative real time PCR. MiRNA-125b-5p was extracted from the plasma samples then Real-time quantitative reversed transcription PCR (RT-qPCR) analysis was done. To analyze miRNA-125b-5p expression in plasma, the ∆Cq value of miRNA-125b-5p was calculated by subtracting Cq of miRNA-125b-5p from the average Cq of MiRNA RNU6B. Stroke patients had significantly higher circulating micro-RNA 125b-5p levels in comparison to healthy controls (P value = 0.01). The circulating levels of micro-RNA 125b-5p were positively correlated with stroke severity assessed by National Institutes of Health Stroke Scale (NIHSS) and infarction size. Stroke patients with poor outcome had significantly higher circulating levels of micro-RNA 125b-5p in comparison to those with good outcome (P value ≤ 0.001). The circulating levels of micro-RNA 125b-5p were significantly higher in patients who developed complications after receiving rt-PA (P value ≤ 0.001). Logistic regression model revealed that each unit increase in micro-RNA125b-5p decreased the odds of good outcome by 0.095 (95% CI 0.016–0.58, P value = 0.011). Plasma micro-RNA 125b-5p is significantly elevated is ischemic stroke patients. It is positively correlated with stroke severity and strongly associated with poor outcome and complications after thrombolytic therapy.
Literature
1.
2.
go back to reference Zivin JA (2009) Acute stroke therapy with tissue plasminogen activator (tPA) since it was approved by the U.S. Food and Drug Administration (FDA). Ann Neurol 66(1):6–10CrossRefPubMed Zivin JA (2009) Acute stroke therapy with tissue plasminogen activator (tPA) since it was approved by the U.S. Food and Drug Administration (FDA). Ann Neurol 66(1):6–10CrossRefPubMed
3.
go back to reference Saver JL, Filip B, Hamilton S, Yanes A, Craig S, Cho M, Conwit R, Starkman S, FAST-MAG Investigators and Coordinators (2010) Improving the reliability of stroke disability grading in clinical trials and clinical practice: the Rankin Focused Assessment (RFA). Stroke. 41(5):992–5CrossRefPubMedPubMedCentral Saver JL, Filip B, Hamilton S, Yanes A, Craig S, Cho M, Conwit R, Starkman S, FAST-MAG Investigators and Coordinators (2010) Improving the reliability of stroke disability grading in clinical trials and clinical practice: the Rankin Focused Assessment (RFA). Stroke. 41(5):992–5CrossRefPubMedPubMedCentral
4.
go back to reference Catanese L, Tarsia J, Fisher M (2017) Acute ischemic stroke therapy overview. Circ Res 120(3):541–558CrossRefPubMed Catanese L, Tarsia J, Fisher M (2017) Acute ischemic stroke therapy overview. Circ Res 120(3):541–558CrossRefPubMed
5.
go back to reference Kanwar JR, Mahidhara G, Kanwar RK (2010) MicroRNA in human cancer and chronic inflammatory diseases. Front Biosci (Schol Ed) 2(3):1113–1126CrossRefPubMed Kanwar JR, Mahidhara G, Kanwar RK (2010) MicroRNA in human cancer and chronic inflammatory diseases. Front Biosci (Schol Ed) 2(3):1113–1126CrossRefPubMed
6.
go back to reference Scherrer N, Fays F, Mueller B, Luft A, Fluri F, Christ-Crain M, Devaux Y, Katan M (2017) MicroRNA 150–5p improves risk classification for mortality within 90 days after acute ischemic stroke. J Stroke 19(3):323–332CrossRefPubMedPubMedCentral Scherrer N, Fays F, Mueller B, Luft A, Fluri F, Christ-Crain M, Devaux Y, Katan M (2017) MicroRNA 150–5p improves risk classification for mortality within 90 days after acute ischemic stroke. J Stroke 19(3):323–332CrossRefPubMedPubMedCentral
7.
go back to reference Dong H, Lei J, Ding L, Wen Y, Ju H, Zhang X (2013) MicroRNA: function, detection, and bioanalysis. Chem Rev 113(8):6207–6233CrossRefPubMed Dong H, Lei J, Ding L, Wen Y, Ju H, Zhang X (2013) MicroRNA: function, detection, and bioanalysis. Chem Rev 113(8):6207–6233CrossRefPubMed
8.
go back to reference Rainer TH, Leung LY, Chan CPY, Leung YK, Abrigo JM, Wang D, Graham CA (2016) Plasma miR-124-3p and miR-16 concentrations as prognostic markers in acute stroke. Clin Biochem 49(9):663–668CrossRefPubMed Rainer TH, Leung LY, Chan CPY, Leung YK, Abrigo JM, Wang D, Graham CA (2016) Plasma miR-124-3p and miR-16 concentrations as prognostic markers in acute stroke. Clin Biochem 49(9):663–668CrossRefPubMed
9.
go back to reference Shen Y, Shen Z, Guo L, Zhang Q, Wang Z, Miao L, Wang M, Wu J, Guo W, Zhu Y (2018) MiR-125b-5p is involved in oxygen and glucose deprivation injury in PC-12 cells via CBS/H2S pathway. Nitric Oxide 1(78):11–21CrossRef Shen Y, Shen Z, Guo L, Zhang Q, Wang Z, Miao L, Wang M, Wu J, Guo W, Zhu Y (2018) MiR-125b-5p is involved in oxygen and glucose deprivation injury in PC-12 cells via CBS/H2S pathway. Nitric Oxide 1(78):11–21CrossRef
10.
go back to reference He XW, Shi YH, Zhao R, Liu YS, Li GF, Hu Y, Chen W, Cui GH, Su JJ, Liu JR (2019) 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 28(6):1654–1661CrossRefPubMed He XW, Shi YH, Zhao R, Liu YS, Li GF, Hu Y, Chen W, Cui GH, Su JJ, Liu JR (2019) 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 28(6):1654–1661CrossRefPubMed
11.
go back to reference He XW, Shi YH, Liu YS, Li GF, Zhao R, Hu Y, Lin CC, Zhuang MT, Su JJ, Liu JR (2019) Increased plasma levels of miR-124-3p, miR-125b-5p and miR-192-5p are associated with outcomes in acute ischemic stroke patients receiving thrombolysis. Atherosclerosis 289:36–43CrossRefPubMed He XW, Shi YH, Liu YS, Li GF, Zhao R, Hu Y, Lin CC, Zhuang MT, Su JJ, Liu JR (2019) Increased plasma levels of miR-124-3p, miR-125b-5p and miR-192-5p are associated with outcomes in acute ischemic stroke patients receiving thrombolysis. Atherosclerosis 289:36–43CrossRefPubMed
12.
go back to reference Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL, American Heart Association Stroke Council (2018) 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 49(3):e46–e110CrossRefPubMed Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL, American Heart Association Stroke Council (2018) 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 49(3):e46–e110CrossRefPubMed
13.
go back to reference Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE III (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke 24(1):35–41CrossRefPubMed Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE III (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke 24(1):35–41CrossRefPubMed
14.
go back to reference National Institute of Neurological Disorders and Stroke (U.S.) (2011) NIH stroke scale. Department of Health and Human Services, NIH National Institute of Neurological Disorders and Stroke (U.S.) (2011) NIH stroke scale. Department of Health and Human Services, NIH
15.
go back to reference Sims JR, Gharai LR, Schaefer PW, Vangel M, Rosenthal ES, Lev MH, Schwamm LH (2009) ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology 72(24):2104–2110CrossRefPubMedPubMedCentral Sims JR, Gharai LR, Schaefer PW, Vangel M, Rosenthal ES, Lev MH, Schwamm LH (2009) ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology 72(24):2104–2110CrossRefPubMedPubMedCentral
16.
go back to reference Banks JL, Marotta CA (2007) Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke 38(3):1091–1096CrossRefPubMed Banks JL, Marotta CA (2007) Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke 38(3):1091–1096CrossRefPubMed
17.
go back to reference Vijayan M, Kumar S, Yin X, Zafer D, Chanana V, Cengiz P, Reddy PH (2018) Identification of novel circulatory microRNA signatures linked to patients with ischemic stroke. Hum Mol Genet 27(13):2318–2329CrossRefPubMedPubMedCentral Vijayan M, Kumar S, Yin X, Zafer D, Chanana V, Cengiz P, Reddy PH (2018) Identification of novel circulatory microRNA signatures linked to patients with ischemic stroke. Hum Mol Genet 27(13):2318–2329CrossRefPubMedPubMedCentral
18.
go back to reference Sepramaniam S, Tan JR, Tan KS, DeSilva DA, Tavintharan S, Woon FP, Wang CW, Yong FL, Karolina DS, Kaur P, Liu FJ, Lim KY, Armugam A, Jeyaseelan K (2014) Circulating microRNAs as biomarkers of acute stroke. Int J Mol Sci 15(1):1418–1432CrossRefPubMedPubMedCentral Sepramaniam S, Tan JR, Tan KS, DeSilva DA, Tavintharan S, Woon FP, Wang CW, Yong FL, Karolina DS, Kaur P, Liu FJ, Lim KY, Armugam A, Jeyaseelan K (2014) Circulating microRNAs as biomarkers of acute stroke. Int J Mol Sci 15(1):1418–1432CrossRefPubMedPubMedCentral
19.
go back to reference Tiedt S, Prestel M, Malik R, Schieferdecker N, Duering M, Kautzky V, Stoycheva I, Böck J, Northoff BH, Klein M, Dorn F, Krohn K, Teupser D, Liesz A, Plesnila N, Holdt LM, Dichgans M (2017) RNA-Seq identifies circulating miR-125a-5p, miR-125b-5p, and miR-143-3p as potential biomarkers for acute ischemic stroke. Circ Res 121(8):970–980CrossRefPubMed Tiedt S, Prestel M, Malik R, Schieferdecker N, Duering M, Kautzky V, Stoycheva I, Böck J, Northoff BH, Klein M, Dorn F, Krohn K, Teupser D, Liesz A, Plesnila N, Holdt LM, Dichgans M (2017) RNA-Seq identifies circulating miR-125a-5p, miR-125b-5p, and miR-143-3p as potential biomarkers for acute ischemic stroke. Circ Res 121(8):970–980CrossRefPubMed
20.
go back to reference Quillinan N, Herson PS, Traystman RJ (2016) Neuropathophysiology of brain injury. Anesthesiol Clin 34(3):453–464CrossRefPubMed Quillinan N, Herson PS, Traystman RJ (2016) Neuropathophysiology of brain injury. Anesthesiol Clin 34(3):453–464CrossRefPubMed
22.
go back to reference Che P, Liu J, Shan Z, Wu R, Yao C, Cui J, Zhu X, Wang J, Burnett MS, Wang S, Wang J (2014) miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1 downregulation. Aging Cell 13(5):926–934CrossRefPubMed Che P, Liu J, Shan Z, Wu R, Yao C, Cui J, Zhu X, Wang J, Burnett MS, Wang S, Wang J (2014) miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1 downregulation. Aging Cell 13(5):926–934CrossRefPubMed
23.
go back to reference Pan W, Zhu S, Dai D, Liu Z, Li D, Li B, Gagliani N, Zheng Y, Tang Y, Weirauch MT, Chen X, Zhu W, Wang Y, Chen B, Qian Y, Chen Y, Fang J, Herbst R, Richman L, Jallal B, Harley JB, Flavell RA, Yao Y, Shen N (2015) MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis. Nat Commun 12(6):7096CrossRef Pan W, Zhu S, Dai D, Liu Z, Li D, Li B, Gagliani N, Zheng Y, Tang Y, Weirauch MT, Chen X, Zhu W, Wang Y, Chen B, Qian Y, Chen Y, Fang J, Herbst R, Richman L, Jallal B, Harley JB, Flavell RA, Yao Y, Shen N (2015) MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis. Nat Commun 12(6):7096CrossRef
24.
go back to reference Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard JM, Mayr A, Weger S, Schett G, Shah A, Boulanger CM, Willeit J, Chowienczyk PJ, Kiechl S, Mayr M (2012) Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol 60(4):290–299CrossRefPubMed Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard JM, Mayr A, Weger S, Schett G, Shah A, Boulanger CM, Willeit J, Chowienczyk PJ, Kiechl S, Mayr M (2012) Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol 60(4):290–299CrossRefPubMed
25.
go back to reference Kaudewitz D, Skroblin P, Bender LH, Barwari T, Willeit P, Pechlaner R, Sunderland NP, Willeit K, Morton AC, Armstrong PC, Chan MV, Lu R, Yin X, Gracio F, Dudek K, Langley SR, Zampetaki A, de Rinaldis E, Ye S, Warner TD, Saxena A, Kiechl S, Storey RF, Mayr M (2016) Association of MicroRNAs and YRNAs With platelet function. Circ Res 118(3):420–432CrossRefPubMed Kaudewitz D, Skroblin P, Bender LH, Barwari T, Willeit P, Pechlaner R, Sunderland NP, Willeit K, Morton AC, Armstrong PC, Chan MV, Lu R, Yin X, Gracio F, Dudek K, Langley SR, Zampetaki A, de Rinaldis E, Ye S, Warner TD, Saxena A, Kiechl S, Storey RF, Mayr M (2016) Association of MicroRNAs and YRNAs With platelet function. Circ Res 118(3):420–432CrossRefPubMed
26.
go back to reference Liu P, Han Z, Ma Q, Liu T, Wang R, Tao Z, Li G, Li F, Zhang S, Li L, Ji X, Zhao H, Luo Y (2019) Upregulation of MicroRNA-128 in the peripheral blood of acute ischemic stroke patients is correlated with stroke severity partially through inhibition of neuronal cell cycle reentry. Cell Transplant 28(7):839–850CrossRefPubMedPubMedCentral Liu P, Han Z, Ma Q, Liu T, Wang R, Tao Z, Li G, Li F, Zhang S, Li L, Ji X, Zhao H, Luo Y (2019) Upregulation of MicroRNA-128 in the peripheral blood of acute ischemic stroke patients is correlated with stroke severity partially through inhibition of neuronal cell cycle reentry. Cell Transplant 28(7):839–850CrossRefPubMedPubMedCentral
27.
go back to reference Wang W, Sun G, Zhang L, Shi L, Zeng Y (2014) Circulating microRNAs as novel potential biomarkers for early diagnosis of acute stroke in humans. J Stroke Cerebrovasc Dis. 23(10):2607–2613CrossRefPubMed Wang W, Sun G, Zhang L, Shi L, Zeng Y (2014) Circulating microRNAs as novel potential biomarkers for early diagnosis of acute stroke in humans. J Stroke Cerebrovasc Dis. 23(10):2607–2613CrossRefPubMed
28.
go back to reference von Engelhardt J, Coserea I, Pawlak V, Fuchs EC, Köhr G, Seeburg PH, Monyer H (2007) Excitotoxicity in vitro by NR2A- and NR2B-containing NMDA receptors. Neuropharmacology 53(1):10–17CrossRef von Engelhardt J, Coserea I, Pawlak V, Fuchs EC, Köhr G, Seeburg PH, Monyer H (2007) Excitotoxicity in vitro by NR2A- and NR2B-containing NMDA receptors. Neuropharmacology 53(1):10–17CrossRef
29.
go back to reference Gui Y, Xu Z, Jin T, Zhang L, Chen L, Hong B, Xie F, Lv W, Hu X (2019) Using extracellular circulating microRNAs to classify the etiological subtypes of ischemic stroke. Transl Stroke Res 10(4):352–361CrossRefPubMed Gui Y, Xu Z, Jin T, Zhang L, Chen L, Hong B, Xie F, Lv W, Hu X (2019) Using extracellular circulating microRNAs to classify the etiological subtypes of ischemic stroke. Transl Stroke Res 10(4):352–361CrossRefPubMed
Metadata
Title
The potential role of micro-RNA 125b-5p level in predicting outcome from thrombolytic therapy in patients with acute ischemic stroke
Authors
Sara Mostafa
Hatem Al Masry
Mona Hussein
Rehab M. Abd Elkareem
Mohammed M. Masoud
Publication date
08-06-2023
Publisher
Springer US
Keyword
Stroke
Published in
Journal of Thrombosis and Thrombolysis / Issue 2/2023
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-023-02831-9

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