Abstract
MicroRNAs (miRNAs) are short sequenced non-coding RNAs that posttranscriptionally regulate gene expression. We investigated circulating miRNA expression levels in acute stroke patients and its relationship with future vascular event. We included acute ischemic stroke patients who admitted to a university hospital between May 1, 2011, and July 31, 2012, and the patients with vascular risk factors but not incident stroke as controls. We collected 5 ml of venous blood, and circulating miRNA levels were evaluated by quantitative real-time polymerase chain reaction. Five miRNAs (miR-17, miR-21, miR-106a, miR-126, and miR-200b), which had been reported to be related to atherosclerosis, were measured. The levels of miRNAs were compared with the presence of acute stroke, vascular risk factors, stroke subtypes, and stroke recurrence after index stroke. A total of 120 patients were included in the study, with 83 acute stroke patients. The levels of miR-17 were significantly increased in acute stroke patients, and the levels of miR-126 had positive correlation with cerebral atherosclerosis (r = 0.254, p = 0.021). Among the 83 stroke patients, eight experienced stroke recurrence during follow-up and higher level of miR-17 was associated with shorter event-free survival (p = 0.047). This study shows that the miR-17 level was elevated in acute ischemic stroke and associated with future stroke recurrence.
Similar content being viewed by others
References
Whiteley W, Wardlaw J, Dennis M, Lowe G, Rumley A, Sattar N, et al. The use of blood biomarkers to predict poor outcome after acute transient ischemic attack or ischemic stroke. Stroke. 2012;43(1):86–91.
Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation. 2006;113(19):2335–62.
Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids—the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011;8(8):467–77.
Liu DZ, Tian Y, Ander BP, Xu H, Stamova BS, Zhan X, et al. Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab. 2010;30(1):92–101.
Tan KS, Armugam A, Sepramaniam S, Lim KY, Setyowati KD, Wang CW, et al. Expression profile of microRNAs in young stroke patients. PLoS ONE. 2009;4(11):e7689. doi:10.1371/journal.pone.0007689.
Lee ST, Chu K, Jung KH, Yoon HJ, Jeon D, Kang KM, et al. MicroRNAs induced during ischemic preconditioning. Stroke. 2010;41(8):1646–51.
Cipollone F, Felicioni L, Sarzani R, Ucchino S, Spigonardo F, Mandolini C, et al. A unique microRNA signature associated with plaque instability in humans. Stroke. 2011;42(9):2556–63.
Adams Jr HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. 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(1):35–41.
Lee EJ, Choi KH, Ryu JS, Jeon SB, Lee SW, Park SW, et al. Stroke risk after coronary artery bypass graft surgery and extent of cerebral artery atherosclerosis. J Am Coll Cardiol. 2011;57(18):1811–8.
Kim JM, Jung KH, Sohn CH, Moon J, Han MH, Roh JK. Middle cerebral artery plaque and prediction of the infarction pattern. Arch Neurol. 2012;69(11):1470–5.
Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet. 2006;38(9):1060–5.
Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, et al. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010;107(5):677–84.
Zhou J, Wang KC, Wu W, Subramaniam S, Shyy JY, Chiu JJ, et al. MicroRNA-21 targets peroxisome proliferators-activated receptor-α in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proc Natl Acad Sci U S A. 2011;108(25):10355–60.
Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MircroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011;13(4):423–33.
Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15(2):261–71.
Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A. 2008;105(5):1516–21.
Nagalla S, Shaw C, Kong X, Kondkar AA, Edelstein LC, Ma L, et al. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood. 2011;117(19):5189–97.
Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010;102(7):1174–9.
Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9.
Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009;324(5935):1710–3.
Hergenreider E, Heydt S, Tréguer K, Boettger T, Horrevoets AJ, Zeiher AM, et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol. 2012;14(3):249–56.
Prakash R, Li W, Qu Z, Johnson MA, Fagan SC, Ergul A. Vascularization pattern after ischemic stroke is different in control versus diabetic rats: relevance to stroke recovery. Stroke. 2013;44(10):2875–82.
Mogilyansky E, Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 2013;20(12):1603–14.
Yu G, Tang JQ, Tian ML, Li H, Wang X, Wu T, et al. Prognostic values of the miR-17-92 cluster and its paralogs in colon cancer. J Surg Oncol. 2012;106(3):232–7.
Moreno PR, Purushothaman KR, Fuster V, Echeverri D, Truszczynska H, Sharma SK, et al. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation. 2004;110(14):2032–8.
Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard JM, et al. Prospective study on circulating microRNAs and the risk of myocardial infarction. J Am Coll Cardiol. 2012;60(4):290–9.
Funding
This work was supported by a grant of the Korea Health technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A111393). The funding has no role in design, collection, analysis, or interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.
Ethical Approval
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional: Seoul National University Hospital, 0906-028-282) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.
Conflict of Interest
Jeong-Min Kim, Keun-Hwa Jung, Kon Chu, Soon-Tae Lee, Jaejun Ban, Jangsup Moon, Manho Kim, Sang Kun Lee, and Jae-Kyu Roh, MD, PhD declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Jeong-Min Kim and Keun-Hwa Jung contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(DOCX 172 kb)
Rights and permissions
About this article
Cite this article
Kim, JM., Jung, KH., Chu, K. et al. Atherosclerosis-Related Circulating MicroRNAs as a Predictor of Stroke Recurrence. Transl. Stroke Res. 6, 191–197 (2015). https://doi.org/10.1007/s12975-015-0390-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12975-015-0390-1