Exosomal miRNAs as Biomarkers of Ischemic Stroke
Abstract
:1. Introduction
2. Exosomes
2.1. Biogenesis and Function
2.2. Isolation Methods and Characterization
3. Ischemic Stroke
Ischemic Stroke Pathogenesis
4. Exosomes in Ischemic Stroke
5. Exosomal miRNAs as Biomarkers of Ischemic Stroke
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Available online: https://www.emro.who.int/health-topics/stroke-cerebrovascular-accident/index.html (accessed on 5 October 2023).
- Unnithan, A.K.A.; Das, J.M.; Mehta, P. Hemorrhagic Stroke; Updated 8 May 2023; StatPearls Publishing: Treasure Island, FL, USA, 2023; Available online: https://www.ncbi.nlm.nih.gov/books/NBK559173/ (accessed on 5 October 2023).
- Makris, K.; Haliassos, A.; Chondrogianni, M.; Tsivgoulis, G. Blood biomarkers in ischemic stroke: Potential role and challenges in clinical practice and research. Crit. Rev. Clin. Lab. Sci. 2018, 55, 294–328. [Google Scholar]
- Mead, G.E.; Sposato, L.A.; Sampaio Silva, G.; Yperzeele, L.; Wu, S.; Kutlubaev, M.; Cheyne, J.; Wahab, K.; Urrutia, V.C.; Sharma, V.K.; et al. A systematic review and synthesis of global stroke guidelines on behalf of the World Stroke Organization. Int. J. Stroke 2023, 18, 499–531. [Google Scholar]
- Dagonnier, M.; Donnan, G.A.; Davis, S.M.; Dewey, H.M.; Howells, D.W. Acute Stroke Biomarkers: Are We There Yet? Front. Neurol. 2021, 12, 619721. [Google Scholar]
- Reymond, S.; Vujić, T.; Sanchez, J.C. Neurovascular Unit-Derived Extracellular Vesicles: From Their Physiopathological Roles to Their Clinical Applications in Acute Brain Injuries. Biomedicines 2022, 10, 2147. [Google Scholar]
- Yokoi, A.; Ochiya, T. Exosomes and extracellular vesicles: Rethinking the essential values in cancer biology. Semin. Cancer Biol. 2021, 74, 79–91. [Google Scholar]
- Théry, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; 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, 1535750. [Google Scholar]
- Lim, W.Q.; Michelle Luk, K.H.; Lee, K.Y.; Nurul, N.; Loh, S.J.; Yeow, Z.X.; Wong, Q.X.; Daniel Looi, Q.H.; Chong, P.P.; How, C.W.; et al. Small Extracellular Vesicles’ miRNAs: Biomarkers and Therapeutics for Neurodegenerative Diseases. Pharmaceutics 2023, 15, 1216. [Google Scholar]
- Delrue, C.; De Bruyne, S.; Speeckaert, R.; Speeckaert, M.M. Urinary Extracellular Vesicles in Chronic Kidney Disease: From Bench to Bedside? Diagnostics 2023, 13, 443. [Google Scholar]
- Wang, H.; Ye, X.; Spanos, M.; Wang, H.; Yang, Z.; Li, G.; Xiao, J.; Zhou, L. Exosomal Non-Coding RNA Mediates Macrophage Polarization: Roles in Cardiovascular Diseases. Biology 2023, 12, 745. [Google Scholar]
- Ghosh, S.; Dhar, R.; Gurudas Shivji, G.; Dey, D.; Devi, A.; Jha, S.K.; Adhikari, M.D.; Gorai, S. Clinical Impact of Exosomes in Colorectal Cancer Metastasis. ACS Appl. Bio Mater. 2023, 6, 2576–2590. [Google Scholar] [CrossRef]
- Chargaff, E. Cell structure and the problem of blood coagulation. J. Biol. Chem. 1945, 160, 351–359. [Google Scholar]
- Wolf, P. The nature and significance of platelet products in human plasma. Br. J. Haematol. 1967, 13, 269–288. [Google Scholar]
- Nunez, E.A.; Wallis, J.; Gershon, M.D. Secretory processes in follicular cells of the bat thyroid. 3. The occurrence of extracellular vesicles and colloid droplets during arousal from hibernation. Am. J. Anat. 1974, 141, 179–201. [Google Scholar]
- Harding, C.; Heuser, J.; Stahl, P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 1983, 97, 329–339. [Google Scholar]
- Pan, B.T.; Johnstone, R.M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell 1983, 33, 967–978. [Google Scholar]
- Couch, Y.; Buzàs, E.I.; Di Vizio, D.; Gho, Y.S.; Harrison, P.; Hill, A.F.; Lötvall, J.; Raposo, G.; Stahl, P.D.; Théry, C.; et al. A brief history of nearly EV-erything—The rise and rise of extracellular vesicles. J. Extracell. Vesicles 2021, 10, e12144. [Google Scholar]
- Lötvall, J.; Hill, A.F.; Hochberg, F.; Buzás, E.I.; Di Vizio, D.; Gardiner, C.; Gho, Y.S.; Kurochkin, I.V.; Mathivanan, S.; Quesenberry, P.; et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles. J. Extracell. Vesicles 2014, 3, 26913. [Google Scholar]
- Huotari, J.; Helenius, A. Endosome maturation. EMBO J. 2011, 30, 3481–3500. [Google Scholar]
- Gao, Y.; Qin, Y.; Wan, C.; Sun, Y.; Meng, J.; Huang, J.; Hu, Y.; Jin, H.; Yang, K. Small Extracellular Vesicles: A Novel Avenue for Cancer Management. Front. Oncol. 2021, 11, 638357. [Google Scholar]
- Lee, R.C.; Feinbaum, R.L.; Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993, 75, 843–854. [Google Scholar]
- Ha, M.; Kim, V.N. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 2014, 15, 509–524. [Google Scholar]
- Dharap, A.; Pokrzywa, C.; Murali, S.; Pandi, G.; Vemuganti, R. MicroRNA miR324-3p induces promoter-mediated expression of RelA gene. PLoS ONE 2013, 8, e79467. [Google Scholar]
- O’Brien, J.; Hayder, H.; Zayedò, Y.; Peng, C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrinol. 2018, 9, 402. [Google Scholar]
- Nik Mohamed Kamal, N.N.S.B.; Shahidan, W.N.S. Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers? Front. Pharmacol. 2020, 10, 1500. [Google Scholar]
- Niu, M.; Li, H.; Li, X.; Yan, X.; Ma, A.; Pan, X.; Zhu, X. Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared with Plasma miRNAs for Large-Artery Atherosclerosis Stroke. Front. Pharmacol. 2021, 12, 791644. [Google Scholar]
- Kalluri, R.; LeBleu, V.S. The biology, function, and biomedical applications of exosomes. Science 2020, 367, eaau6977. [Google Scholar]
- Słomka, A.; Kornek, M.; Cho, W.C. Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review. Cells 2022, 11, 2913. [Google Scholar]
- Feng, L.; Guo, L.; Tanaka, Y.; Su, L. Tumor-Derived Small Extracellular Vesicles Involved in Breast Cancer Progression and Drug Resistance. Int. J. Mol. Sci. 2022, 23, 15236. [Google Scholar]
- Nezhad Nezhad, M.T.; Rajabi, M.; Nekooeizadeh, P.; Sanjari, S.; Pourvirdi, B.; Heidari, M.M.; Veradi Esfahani, P.; Abdoli, A.; Bagheri, S.; Tobeiha, M. Systemic lupus erythematosus: From non-coding RNAs to exosomal non-coding RNAs. Pathol. Res. Pr. 2022, 247, 154508. [Google Scholar]
- Sufianov, A.; Kostin, A.; Begliarzade, S.; Kudriashov, V.; Ilyasova, T.; Liang, Y.; Mukhamedzyanov, A.; Beylerli, O. Exosomal noncoding RNAs as a novel target for diabetes mellitus and its complications. Noncoding RNA Res. 2023, 8, 192–204. [Google Scholar]
- Lin, S.; Yu, Z.; Chen, D.; Wang, Z.; Miao, J.; Li, Q. Progress in Microfluidics-Based Exosome Separation and Detection Technologies for Diagnostic Applications. Small 2020, 16, 1903916. [Google Scholar]
- Zhang, P.; Zhou, X.; He, M.; Shang, Y.; Tetlow, A.L.; Godwin, A.K.; Zeng, Y. Ultrasensitive detection of circulating exosomes with a 3D-nanopatterned microfluidic chip. Nat. Biomed. Eng. 2019, 3, 438–451. [Google Scholar]
- Tauro, B.J.; Greening, D.W.; Mathias, R.A.; Ji, H.; Mathivanan, S.; Scott, A.M.; Simpson, R.J. Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 2012, 56, 293–304. [Google Scholar]
- Chen, P.H.; Gao, S.; Wang, Y.J.; Xu, A.D.; Li, Y.S.; Wang, D. Classifying Ischemic Stroke, from TOAST to CISS. CNS Neurosci. Ther. 2012, 18, 452–456. [Google Scholar]
- Guan, S.; Yu, H.; Yan, G.; Gao, M.; Sun, W.; Zhang, X. Characterization of Urinary Exosomes Purified with Size Exclusion Chromatography and Ultracentrifugation. J. Proteom. Res. 2020, 19, 2217–2225. [Google Scholar]
- Oeyen, E.; Van Mol, K.; Baggerman, G.; Willems, H.; Boonen, K.; Rolfo, C.; Pauwels, P.; Jacobs, A.; Schildermans, K.; Cho, W.C.; et al. Ultrafiltration and size exclusion chromatography combined with asymmetrical-flow field-flow fractionation for the isolation and characterisation of extracellular vesicles from urine. J. Extracell. Vesicles 2018, 7, 1490143. [Google Scholar]
- Ruivo, C.F.; Adem, B.; Silva, M.; Melo, S.A. The Biology of Cancer Exosomes: Insights and New Perspectives. Cancer Res. 2017, 77, 6480–6488. [Google Scholar]
- Niu, Z.; Pang, R.T.K.; Liu, W.; Li, Q.; Cheng, R.; Yeung, W.S.B. Polymer-based precipitation preserves biological activities of extracellular vesicles from an endometrial cell line. PLoS ONE 2017, 12, e0186534. [Google Scholar]
- Moon, S.; Shin, D.W.; Kim, S.; Lee, Y.S.; Mankhong, S.; Yang, S.W.; Lee, P.H.; Park, D.H.; Kwak, H.B.; Lee, J.S.; et al. Enrichment of Exosome-Like Extracellular Vesicles from Plasma Suitable for Clinical Vesicular miRNA Biomarker Research. J. Clin. Med. 2019, 8, 1995. [Google Scholar]
- Witwer, K.W.; Buzás, E.I.; Bemis, L.T.; Bora, A.; Lässer, C.; Lötvall, J.; Nolte-’t Hoen, E.N.; Piper, M.G.; Sivaraman, S.; Skog, J.; et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J. Extracell. Vesicles 2013, 2, 20360. [Google Scholar] [CrossRef]
- Szatanek, R.; Baran, J.; Siedlar, M.; Baj-Krzyworzeka, M. Isolation of extracellular vesicles: Determining the correct approach (Review). Int. J. Mol. Med. 2015, 36, 11–17. [Google Scholar]
- Chen, S.; Sun, F.; Qian, H.; Xu, W.; Jiang, J. Preconditioning and Engineering Strategies for Improving the Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Cell-Free Therapy. Stem Cells Int. 2022, 2022, 1779346. [Google Scholar]
- Liu, W.Z.; Ma, Z.J.; Kang, X.W. Current status and outlook of advances in exosome isolation. Anal. Bioanal. Chem. 2022, 414, 7123–7141. [Google Scholar]
- Kuriakose, D.; Xiao, Z. Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives. Int. J. Mol. Sci. 2020, 21, 7609. [Google Scholar]
- Tuttolomondo, A. Immunoinflammatory Background of Neuronal Damage in Stroke. Int. J. Mol. Sci. 2023, 24, 8619. [Google Scholar]
- Pacinella, G.; Ciaccio, A.M.; Tuttolomondo, A. Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases. Int. J. Mol. Sci. 2022, 23, 5722. [Google Scholar]
- Puleo, M.G.; Miceli, S.; Di Chiara, T.; Pizzo, G.M.; Della Corte, V.; Simonetta, I.; Pinto, A.; Tuttolomondo, A. Molecular Mechanisms of Inflammasome in Ischemic Stroke Pathogenesis. Pharmaceuticals 2022, 15, 1168. [Google Scholar]
- Khoshnam, S.E.; Winlow, W.; Farzaneh, M.; Farbood, Y.; Moghaddam, H.F. Pathogenic mechanisms following ischemic stroke. Neurol. Sci. 2017, 7, 1167–1186. [Google Scholar] [CrossRef]
- Shen, X.Y.; Gao, Z.K.; Han, Y.; Yuan, M.; Guo, Y.S.; Bi, X. Activation and Role of Astrocytes in Ischemic Stroke. Front. Cell Neurosci. 2021, 15, 755955. [Google Scholar]
- Sofroniew, M.V.; Vinters, H.V. Astrocytes: Biology and pathology. Acta Neuropathol. 2010, 119, 7–35. [Google Scholar]
- Gharbi, T.; Zhang, Z.; Yang, G.Y. The Function of Astrocyte Mediated Extracellular Vesicles in Central Nervous System Diseases. Front. Cell Dev. Biol. 2020, 8, 568889. [Google Scholar]
- Pei, X.; Li, Y.; Zhu, L.; Zhou, Z. Astrocyte-derived exosomes suppress autophagy and ameliorate neuronal damage in experimental ischemic stroke. Exp. Cell Res. 2019, 382, 111474. [Google Scholar]
- Bu, X.; Li, D.; Wang, F.; Sun, Q.; Zhang, Z. Protective role of astrocyte-derived exosomal microRNA-361 in cerebral ischemic-reperfusion injury by regulating the AMPK/mTOR signaling pathway and targeting CTSB. Neuropsychiatr. Dis. Treat. 2020, 16, 1863–1877. [Google Scholar]
- Wu, W.; Liu, J.; Yang, C.; Xu, Z.; Huang, J.; Lin, J. Astrocyte-derived exosome-transported microRNA-34c is neuroprotective against cerebral ischemia/reperfusion injury via TLR7 and the NF-kappaB/MAPK pathways. Brain Res. Bull. 2020, 163, 84–94. [Google Scholar]
- Xin, H.; Li, Y.; Liu, Z.; Wang, X.; Shang, X.; Cui, Y.; Zhang, Z.G.; Chopp, M. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosomeenriched extracellular particles. Stem Cells 2013, 31, 2737–2746. [Google Scholar]
- Pascua-Maestro, R.; Gonzalez, E.; Lillo, C.; Ganfornina, M.D.; Falcon-Perez, J.M.; Sanchez, D. Extracellular vesicles secreted by astroglial cells transport apolipoprotein D to neurons and mediate neuronal survival upon oxidative stress. Front. Cell Neurosci. 2018, 12, 526. [Google Scholar]
- Harris, M.G.; Hulseberg, P.; Ling, C.; Karman, J.; Clarkson, B.D.; Harding, J.S.; Zhang, M.; Sandor, A.; Christensen, K.; Nagy, A.; et al. Immune privilege of the CNS is not the consequence of limited antigen sampling. Sci. Rep. 2014, 4, 4422. [Google Scholar]
- Liu, G.; Li, T.; Yang, A.; Zhang, X.; Qi, S.; Feng, W. Knowledge domains and emerging trends of microglia research from 2002 to 2021: A bibliometric analysis and visualization study. Front Aging Neurosci. 2023, 14, 1057214. [Google Scholar]
- Dong, R.; Huang, R.; Wang, J.; Liu, H.; Xu, Z. Effects of Microglial Activation and Polarization on Brain Injury After Stroke. Front. Neurol. 2021, 12, 620948. [Google Scholar]
- Jiang, C.T.; Wu, W.F.; Deng, Y.H.; Ge, J.W. Modulators of Microglia Activation and Polarization in Ischemic Stroke. Mol. Med. Rep. 2020, 21, 2006–2018. [Google Scholar]
- Song, Y.; Li, Z.; He, T.; Qu, M.; Jiang, L.; Li, W.; Shi, X.; Pan, J.; Zhang, L.; Wang, Y.; et al. M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124. Theranostics 2019, 9, 2910–2923. [Google Scholar]
- Zhang, D.; Cai, G.; Liu, K.; Zhuang, Z.; Jia, K.; Pei, S.; Wang, X.; Wang, H.; Xu, S.; Cui, C.; et al. Microglia exosomal miRNA-137 attenuates ischemic brain injury through targeting Notch1. Aging 2021, 13, 4079–4095. [Google Scholar]
- Xie, L.; Zhao, H.; Wang, Y.; Chen, Z. Exosomal shuttled miR-424-5p from ischemic preconditioned microglia mediates cerebral endothelial cell injury through negatively regulation of FGF2/STAT3 pathway. Exp. Neurol. 2020, 333, 113411. [Google Scholar]
- Li, F.; Kang, X.; Xin, W.; Li, X. The Emerging Role of Extracellular Vesicle Derived from Neurons/Neurogliocytes in Central Nervous System Diseases: Novel Insights Into Ischemic Stroke. Front. Pharmacol. 2022, 13, 890698. [Google Scholar]
- Norris, G.T.; Smirnov, I.; Filiano, A.J.; Shadowen, H.M.; Cody, K.R.; Thompson, J.A.; Harris, T.H.; Gaultier, A.; Overall, C.C.; Kipnis, J. Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury. J. Exp. Med. 2018, 215, 1789–1801. [Google Scholar]
- Pluvinage, J.V.; Haney, M.S.; Smith, B.A.H.; Sun, J.; Iram, T.; Bonanno, L.; Li, L.; Lee, D.P.; Morgens, D.W.; Yang, A.C.; et al. CD22 blockade restores homeostatic microglial phagocytosis in ageing brains. Nature 2019, 56, 187–192. [Google Scholar]
- Zhao, B.; Fei, Y.; Zhu, J.; Yin, Q.; Fang, W.; Li, Y. PAF Receptor Inhibition Attenuates Neuronal Pyroptosis in Cerebral Ischemia/Reperfusion Injury. Mol. Neurobiol. 2021, 58, 6520–6539. [Google Scholar]
- Yang, M.; Weng, T.; Zhang, W.; Zhang, M.; He, X.; Han, C.; Wang, X. The Roles of Non-coding RNA in the Development and Regeneration of Hair Follicles: Current Status and Further Perspectives. Front. Cell Dev. Biol. 2021, 9, 720879. [Google Scholar]
- Domingues, H.S.; Falcão, A.M.; Mendes-Pinto, I.; Salgado, A.J.; Teixeira, F.G. Exosome Circuitry During (De)(Re)Myelination of the Central Nervous System. Front. Cell Dev. Biol. 2020, 8, 483. [Google Scholar]
- Frühbeis, C.; Kuo-Elsner, W.P.; Müller, C.; Barth, K.; Peris, L.; Tenzer, S.; Möbius, W.; Werner, H.B.; Nave, K.A.; Fröhlich, D.; et al. Oligodendrocytes support axonal transport and maintenance via exosome secretion. PLoS Biol. 2020, 18, e3000621. [Google Scholar]
- Fröhlich, D.; Kuo, W.P.; Frühbeis, C.; Sun, J.J.; Zehendner, C.M.; Luhmann, H.J.; Pinto, S.; Toedling, J.; Trotter, J.; Krämer-Albers, E.M. Multifaceted effects of oligodendroglial exosomes on neurons: Impact on neuronal firing rate, signal transduction and gene regulation. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2014, 369, 20130510. [Google Scholar]
- Sun, J.; Yuan, Q.; Guo, L.; Xiao, G.; Zhang, T.; Liang, B.; Yao, R.; Zhu, Y.; Li, Y.; Hu, L. Brain Microvascular Endothelial Cell-Derived Exosomes Protect Neurons from Ischemia–Reperfusion Injury in Mice. Pharmaceuticals 2022, 15, 1287. [Google Scholar]
- Hermann, D.M.; Popa-Wagner, A.; Kleinschnitz, C.; Doeppner, T.R. Animal models of ischemic stroke and their impact on drug discovery. Expert. Opin. Drug Discov. 2019, 14, 315–326. [Google Scholar]
- Zhou, J.; Chen, L.; Chen, B.; Huang, S.; Zeng, C.; Wu, H.; Chen, C.; Long, F. Increased serum exosomal miR-134 expression in the acute ischemic stroke patients. BMC Neurol. 2018, 18, 198. [Google Scholar]
- Chen, Y.; Song, Y.; Huang, J.; Qu, M.; Zhang, Y.; Geng, J.; Zhang, Z.; Liu, J.; Yang, G.Y. Increased Circulating Exosomal miRNA-223 Is Associated with Acute Ischemic Stroke. Front. Neurol. 2017, 8, 57. [Google Scholar]
- Jiang, S.; Wu, J.; Geng, Y.; Zhang, Y.; Wang, Y.; Wu, J.; Lu, C.; Luo, G.; Zan, J.; Zhang, Y. Identification of Differentially Expressed microRNAs Associated with Ischemic Stroke by Integrated Bioinformatics Approaches. Int. J. Genom. 2022, 2022, 9264555. [Google Scholar]
- Ji, Q.; Ji, Y.; Peng, J.; Zhou, X.; Chen, X.; Zhao, H.; Xu, T.; Chen, L.; Xu, Y. Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients. PLoS ONE 2016, 11, e0163645. [Google Scholar]
- Qi, Z.; Zhao, Y.; Su, Y.; Cao, B.; Yang, J.J.; Xing, Q. Serum Extracellular Vesicle-Derived miR-124-3p as a Diagnostic and Predictive Marker for Early-Stage Acute Ischemic Stroke. Front. Mol. Biosci. 2021, 8, 685088. [Google Scholar]
- Kalani, M.Y.S.; Alsop, E.; Meechoovet, B.; Beecroft, T.; Agrawal, K.; Whitsett, T.G.; Huentelman, M.J.; Spetzler, R.F.; Nakaji, P.; Kim, S.; et al. Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes. J. Extracell. Vesicles 2020, 9, 1713540. [Google Scholar]
- Song, P.; Sun, H.; Chen, H.; Wang, Y.; Zhang, Q. Decreased Serum Exosomal miR-152-3p Contributes to the Progression of Acute Ischemic Stroke. Clin. Lab. 2020, 66, 1615–1622. [Google Scholar] [CrossRef]
- Wang, S.; Jun, J.; Cong, L.; Du, L.; Wang, C. miR-328-3p, a Predictor of Stroke, Aggravates the Cerebral Ischemia-Reperfusion Injury. Int. J. Gen. Med. 2021, 14, 2367–2376. [Google Scholar]
- He, X.W.; Shi, Y.H.; Zhao, R.; Liu, Y.S.; Li, G.F.; Hu, Y.; Chen, W.; Cui, G.H.; Su, J.J.; Liu, J.R. 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, 1654–1661. [Google Scholar]
- Allen, L.M.; Hasso, A.N.; Handwerker, J.; Farid, H. Sequence-specific MR imaging findings that are useful in dating ischemic stroke. Radiographics 2012, 32, 1285–1299. [Google Scholar]
- Wang, W.; Li, D.B.; Li, R.Y.; Zhou, X.; Yu, D.J.; Lan, X.Y.; Li, J.P.; Liu, J.L. Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p. Cerebrovasc. Dis. 2018, 45, 204–212. [Google Scholar]
- Li, D.B.; Liu, J.L.; Wang, W.; Li, R.Y.; Yu, D.J.; Lan, X.Y.; Li, J.P. Plasma Exosomal miR-422a and miR-125b-2-3p Serve as Biomarkers for Ischemic Stroke. Curr. Neurovasc. Res. 2017, 14, 330–337. [Google Scholar]
- Adams, H.P., Jr.; Bendixen, B.H.; Kappelle, L.J.; Biller, J.; Love, B.B.; Gordon, D.L.; Marsh, E.E. 3rd 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 1993, 24, 35–41. [Google Scholar]
- Van Kralingen, J.C.; McFall, A.; Ord, E.N.J.; Coyle, T.F.; Bissett, M.; McClure, J.D.; McCabe, C.; Macrae, I.M.; Dawson, J.; Work, L.M. Altered Extracellular Vesicle MicroRNA Expression in Ischemic Stroke and Small Vessel Disease. Transl. Stroke Res. 2019, 10, 495–508. [Google Scholar]
- Otero-Ortega, L.; Alonso-López, E.; Pérez-Mato, M.; Laso-García, F.; Gómez-de Frutos, M.C.; Diekhorst, L.; García-Bermejo, M.L.; Conde-Moreno, E.; Fuentes, B.; de Leciñana, M.A.; et al. Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke. Biomedicines 2021, 9, 786. [Google Scholar]
- Felekkis, K.; Pieri, M.; Papaneophytou, C. Variability in the levels of exosomal miRNAs among human subjects could be explained by differential interactions of exosomes with the endothelium. IUBMB Life 2021, 73, 1400–1405. [Google Scholar]
- Sullivan, R.; Montgomery, A.; Scipioni, A.; Jhaveri, P.; Schmidt, A.T.; Hicks, S.D. Confounding Factors Impacting microRNA Expression in Human Saliva: Methodological and Biological Considerations. Genes 2022, 13, 1874. [Google Scholar]
- Guo, L.; Zhang, Q.; Ma, X.; Wang, J.; Liang, T. miRNA and mRNA expression analysis reveals potential sex-biased miRNA expression. Sci. Rep. 2017, 7, 39812. [Google Scholar]
- Sharma, S.; Eghbali, M. Influence of sex differences on microRNA gene regulation in disease. Biol. Sex. Differ. 2014, 5, 3. [Google Scholar]
- Iacomino, G.; Siani, A. Role of microRNAs in obesity and obesity-related diseases. Genes. Nutr. 2017, 12, 23. [Google Scholar]
- Mantilla-Escalante, D.C.; de las Hazas, M.C.L.; Gil-Zamorano, J.; del Pozo-Acebo, L.; Crespo, M.C.; Martín-Hernández, R.; del Saz, A.; Tomé-Carneiro, J.; Cardona, F.; Cornejo-Pareja, I.; et al. Postprandial Circulating miRNAs in Response to a Dietary Fat Challenge. Nutrients 2019, 11, 1326. [Google Scholar]
- Telles, G.D.; Libardi, C.A.; Conceição, M.S.; Vechin, F.C.; Lixandrão, M.E.; De Andrade, A.L.L.; Guedes, D.N.; Ugrinowitsch, C.; Camera, D.M. Time Course of Skeletal Muscle miRNA Expression after Resistance, High-Intensity Interval, and Concurrent Exercise. Med. Sci. Sports Exerc. 2021, 53, 1708–1718. [Google Scholar]
- Zhou, Q.; Shi, C.; Lv, Y.; Zhao, C.; Jiao, Z.; Wang, T. Circulating microRNAs in Response to Exercise Training in Healthy Adults. Front. Genet. 2020, 11, 256. [Google Scholar]
Authors | Study Population | Time Sample Collection of Stroke Onset | Exosomal miRNA | AUC | Sensitivity | Specificity |
---|---|---|---|---|---|---|
Zhou et al. [75] | 50 patients and 50 controls | Within 24 h | miR-134 | 0.834 (0.88–0.97) | 75.3% | 72.8% |
Chen et al. [76] | 50 patients and 33 controls | Within 72 h | miRNA-223 | 0.859 | 84% | 78.8% |
Ji et al. [78] | 65 patients and 66 controls | NA | miR-9 and miR-124 | miR-9: 0.8026 (0.7235–0.8816) miR-124: 0.6976 (0.6506–0.7895) | NA | NA |
Kalani et al. [80] | 21 patients with ischemic stroke and 36 patients with hemorrhagic stroke | Within 24 h | miR-27b-3p and miR-146b-5p | NA | NA | NA |
Qi et al. [79] | 10 patients and 10 controls | At 2 h, 4 h, and 6 h | miR-124-3p | At 2 h: 0.81 At 4 h: 0.90 At 6 h: 0.94 | NA | NA |
Song et al. [81] | 93 patients and 70 controls | NA | miR-152-3p | 0.935 (0.826–0.998) | 92.54% | 94.19% |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ciaccio, A.M.; Tuttolomondo, A. Exosomal miRNAs as Biomarkers of Ischemic Stroke. Brain Sci. 2023, 13, 1647. https://doi.org/10.3390/brainsci13121647
Ciaccio AM, Tuttolomondo A. Exosomal miRNAs as Biomarkers of Ischemic Stroke. Brain Sciences. 2023; 13(12):1647. https://doi.org/10.3390/brainsci13121647
Chicago/Turabian StyleCiaccio, Anna Maria, and Antonino Tuttolomondo. 2023. "Exosomal miRNAs as Biomarkers of Ischemic Stroke" Brain Sciences 13, no. 12: 1647. https://doi.org/10.3390/brainsci13121647
APA StyleCiaccio, A. M., & Tuttolomondo, A. (2023). Exosomal miRNAs as Biomarkers of Ischemic Stroke. Brain Sciences, 13(12), 1647. https://doi.org/10.3390/brainsci13121647