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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Research Article

Metabolic Adjustments by LncRNAs in Peripheral Neutrophils Partly Account for the Complete Compensation of Asymptomatic MMD Patients

Author(s): Ziping Han, Lingzhi Li, Ping Liu, Yuyou Huang, Sijia Zhang, Guangwen Li, Fangfang Li, Haiping Zhao, Zhen Tao, Rongliang Wang, Qingfeng Ma* and Yumin Luo*

Volume 19, Issue 4, 2020

Page: [306 - 317] Pages: 12

DOI: 10.2174/1871527319666200618150827

Price: $65

Abstract

Background: Due to the recent development of non-invasive examinations, more asymptomatic patients with Moyamoya Disease (MMD) have been diagnosed than ever. However, its underlying molecular mechanisms and clinical intervention guidelines are all still obscure.

Methods: Microarray was used to explore those differentially expressed mRNAs and lncRNAs in peripheral neutrophils of asymptomatic MMD patients. Then enrichment analyses based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for those differentially expressed mRNAs and lncRNA associated mRNAs were performed for underlying molecular mechanisms.

Results: Here, we identified a total of 2824 differentially expressed lncRNAs and 522 differentially expressed mRNAs (fold change > 2 and P<0.05) in peripheral neutrophils of asymptomatic MMD patients, compared with healthy controls. Then enrichment analyses based on GO and KEGG showed that the neighboring protein-coding mRNAs of those up-regulated and down-regulated lncRNAs were mainly involved in distinct metabolic processes respectively, which may act as a complementary response to insufficient blood supplies in MMD. Further enrichment analyses of those differentially expressed mRNAs preferentially listed essential physiological processes such as peptide cross-linking, chromatin assembly among others. Moreover, altered mRNAs also revealed to be enriched in renin secretion, platelet activation, inflammation and others.

Conclusion: We demonstrated for the first time that metabolic adjustments by dysregulated lncRNAs in peripheral neutrophils might partially account for the complete compensation of asymptomatic MMD patients. In addition, more attention should be paid on renin secretion and platelet activation in order to better understand the pathogenesis and guide clinical intervention for asymptomatic MMDs.

Keywords: LncRNAs, neutrophils, microarray, moyamoya disease, asymptomatic, bioinformatics.

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[1]
Kleinloog R, Regli L, Rinkel GJ, Klijn CJ. Regional differences in incidence and patient characteristics of moyamoya disease: a systematic review. J Neurol Neurosurg Psychiatry 2012; 83(5): 531-6.
[http://dx.doi.org/10.1136/jnnp-2011-301387] [PMID: 22378916]
[2]
Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009; 360(12): 1226-37.
[http://dx.doi.org/10.1056/NEJMra0804622] [PMID: 19297575]
[3]
Bang OY, Fujimura M, Kim SK. The pathophysiology of moyamoya disease: an update. J Stroke 2016; 18(1): 12-20.
[http://dx.doi.org/10.5853/jos.2015.01760] [PMID: 26846756]
[4]
Cecchi AC, Guo D, Ren Z, et al. RNF213 rare variants in an ethnically diverse population with moyamoya disease. Stroke 2014; 45(11): 3200-7.
[http://dx.doi.org/10.1161/STROKEAHA.114.006244] [PMID: 25278557]
[5]
Takagi Y, Kikuta K, Nozaki K, Hashimoto N. Histological features of middle cerebral arteries from patients treated for moyamoya disease. Neurol Med Chir (Tokyo) 2007; 47(1): 1-4.
[http://dx.doi.org/10.2176/nmc.47.1] [PMID: 17245006]
[6]
Takagi Y, Kikuta K, Sadamasa N, Nozaki K, Hashimoto N. Proliferative activity through extracellular signal-regulated kinase of smooth muscle cells in vascular walls of cerebral arteriovenous malformations. Neurosurgery 2006; 58(4): 740-8.
[http://dx.doi.org/10.1227/01.NEU.0000192167.54627.3A] [PMID: 16575338]
[7]
Kuroda S, Group AS. AMORE Study Group Asymptomatic moyamoya disease: literature review and ongoing AMORE study. Neurol Med Chir (Tokyo) 2015; 55(3): 194-8.
[http://dx.doi.org/10.2176/nmc.ra.2014-0305] [PMID: 25739434]
[8]
Shinkawa A, Ueda K, Kiyohara Y, et al. Silent cerebral infarction in a community-based autopsy series in Japan. The Hisayama Study. Stroke 1995; 26(3): 380-5.
[http://dx.doi.org/10.1161/01.STR.26.3.380] [PMID: 7886710]
[9]
Kikuta K, Takagi Y, Nozaki K, et al. Asymptomatic microbleeds in moyamoya disease: T2*-weighted gradient-echo magnetic resonance imaging study. J Neurosurg 2005; 102(3): 470-5.
[http://dx.doi.org/10.3171/jns.2005.102.3.0470] [PMID: 15796381]
[10]
Kuroda S, Hashimoto N, Yoshimoto T, Iwasaki Y. Radiological findings, clinical course, and outcome in asymptomatic moyamoya disease: results of multicenter survey in Japan. Stroke 2007; 38(5): 1430-5.
[http://dx.doi.org/10.1161/STROKEAHA.106.478297] [PMID: 17395863]
[11]
Derrien T, Johnson R, Bussotti G, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 2012; 22(9): 1775-89.
[http://dx.doi.org/10.1101/gr.132159.111] [PMID: 22955988]
[12]
Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell 2013; 154(1): 26-46.
[http://dx.doi.org/10.1016/j.cell.2013.06.020] [PMID: 23827673]
[13]
Heward JA, Lindsay MA. Long non-coding RNAs in the regulation of the immune response. Trends Immunol 2014; 35(9): 408-19.
[http://dx.doi.org/10.1016/j.it.2014.07.005] [PMID: 25113636]
[14]
Kang HS, Kim JH, Phi JH, et al. Plasma matrix metalloproteinases, cytokines and angiogenic factors in moyamoya disease. J Neurol Neurosurg Psychiatry 2010; 81(6): 673-8.
[http://dx.doi.org/10.1136/jnnp.2009.191817] [PMID: 19965844]
[15]
Gao F, Yu L, Zhang D, Zhang Y, Wang R, Zhao J. Long Noncoding RNAs and Their Regulatory Network: Potential Therapeutic Targets for Adult moyamoya Disease. World Neurosurg 2016; 93: 111-9.
[http://dx.doi.org/10.1016/j.wneu.2016.05.081] [PMID: 27268316]
[16]
Wang W, Gao F, Zhao Z, et al. Integrated analysis of LncRNA-mRNA co-expression profiles in patients with moyamoya disease. Sci Rep 2017; 7: 42421.
[http://dx.doi.org/10.1038/srep42421] [PMID: 28176861]
[17]
Seignez C, Phillipson M. The multitasking neutrophils and their involvement in angiogenesis. Curr Opin Hematol 2017; 24(1): 3-8.
[http://dx.doi.org/10.1097/MOH.0000000000000300] [PMID: 27755126]
[18]
Massena S, Christoffersson G, Vågesjö E, et al. Identification and characterization of VEGF-A-responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans. Blood 2015; 126(17): 2016-26.
[http://dx.doi.org/10.1182/blood-2015-03-631572] [PMID: 26286848]
[19]
Christoffersson G, Vågesjö E, Vandooren J, et al. VEGF-A recruits a proangiogenic MMP-9-delivering neutrophil subset that induces angiogenesis in transplanted hypoxic tissue. Blood 2012; 120(23): 4653-62.
[http://dx.doi.org/10.1182/blood-2012-04-421040] [PMID: 22966168]
[20]
Rivera LB, Bergers G. Intertwined regulation of angiogenesis and immunity by myeloid cells. Trends Immunol 2015; 36(4): 240-9.
[http://dx.doi.org/10.1016/j.it.2015.02.005] [PMID: 25770923]
[21]
Avraham-Davidi I, Yona S, Grunewald M, et al. On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells. J Exp Med 2013; 210(12): 2611-25.
[http://dx.doi.org/10.1084/jem.20120690] [PMID: 24166715]
[22]
Ma Q, Li L, Yu B, et al. Circular RNA profiling of neutrophil transcriptome provides insights into asymptomatic moyamoya disease. Brain Res 2019; 1719: 104-12.
[http://dx.doi.org/10.1016/j.brainres.2019.05.033] [PMID: 31132337]
[23]
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet 2009; 10(3): 155-9.
[http://dx.doi.org/10.1038/nrg2521] [PMID: 19188922]
[24]
Nanba R, Kuroda S, Takeda M, et al. Clinical features and outcomes of 10 asymptomatic adult patients with moyamoya disease. No Shinkei Geka 2003; 31(12): 1291-5.
[PMID: 14719442]
[25]
Takahashi M. Magnification angiography in moyamoya disease: new observations on collateral vessels. Radiology 1980; 136(2): 379-86.
[http://dx.doi.org/10.1148/radiology.136.2.7403514] [PMID: 7403514]
[26]
Suzuki J, Kodama N. Moyamoya disease--a review. Stroke 1983; 14(1): 104-9.
[http://dx.doi.org/10.1161/01.STR.14.1.104] [PMID: 6823678]
[27]
Podsiedlik M, Markowicz-Piasecka M, Mikiciuk-Olasik E, Sikora J. The associations between central nervous system diseases and haemostatic disorders. CNS Neurol Disord Drug Targets 2019; 18(4): 307-16.
[http://dx.doi.org/10.2174/1871527318666190314101946] [PMID: 30868969]
[28]
Mohammadi F, Nezafat N, Negahdaripour M, et al. Neuroprotective effects of heat shock protein 70. CNS Neurol Disord Drug Targets 2018; 17(10): 736-42.
[http://dx.doi.org/10.2174/1871527317666180827111152] [PMID: 30147017]
[29]
Wang S, Ma F, Huang L, et al. Dl-3-n-Butylphthalide (NBP): a promising therapeutic agent for ischemic stroke. CNS Neurol Disord Drug Targets 2018; 17(5): 338-47.
[http://dx.doi.org/10.2174/1871527317666180612125843] [PMID: 29895257]
[30]
Gong Z, Pan J, Li X, Wang H, He L, Peng Y. Hydroxysafflor yellow A reprograms TLR9 signalling pathway in ischaemic cortex after cerebral ischaemia and reperfusion. CNS Neurol Disord Drug Targets 2018; 17(5): 370-82.
[http://dx.doi.org/10.2174/1871527317666180502110205] [PMID: 29732997]
[31]
Catalin B, Rogoveanu OC, Pirici I, et al. Cerebrolysin and aquaporin 4 inhibition improve pathological and motor recovery after ischemic stroke. CNS Neurol Disord Drug Targets 2018; 17(4): 299-308.
[http://dx.doi.org/10.2174/1871527317666180425124340] [PMID: 29692268]
[32]
Arshad N, Lin TS, Yahaya MF. Metabolic syndrome and its effect on the brain: possible mechanism. CNS Neurol Disord Drug Targets 2018; 17(8): 595-603.
[http://dx.doi.org/10.2174/1871527317666180724143258] [PMID: 30047340]
[33]
Ferrè F, Colantoni A, Helmer-Citterich M. Revealing protein-lncRNA interaction. Brief Bioinform 2016; 17(1): 106-16.
[http://dx.doi.org/10.1093/bib/bbv031] [PMID: 26041786]
[34]
Xu J, Zhang F, Gao C, et al. Microarray analysis of lncRNA and mRNA expression profiles in patients with neuromyelitis optica. Mol Neurobiol 2017; 54(3): 2201-8.
[http://dx.doi.org/10.1007/s12035-016-9754-0] [PMID: 26941100]
[35]
Wang D, Gu C, Liu M, Liu G, Liu H, Wang Y. Analysis of long noncoding RNA expression profile in human pulmonary microvascular endothelial cells exposed to lipopolysaccharide. Cell Physiol Biochem 2019; 52(4): 653-67.
[http://dx.doi.org/10.33594/000000046] [PMID: 30921505]
[36]
Li L, Wang P, Zhao H, Luo Y. Noncoding RNAs and intracerebral hemorrhage. CNS Neurol Disord Drug Targets 2019; 18(3): 205-11.
[http://dx.doi.org/10.2174/1871527318666190204102604] [PMID: 30714535]
[37]
Forouzanfar F, Shojapour M, Asgharzade S, Amini E. Causes and consequences of MicroRNA dysregulation following cerebral ischemia-reperfusion injury. CNS Neurol Disord Drug Targets 2019; 18(3): 212-21.
[http://dx.doi.org/10.2174/1871527318666190204104629] [PMID: 30714533]
[38]
Chen Y, Zhou J. LncRNAs: macromolecules with big roles in neurobiology and neurological diseases. Metab Brain Dis 2017; 32(2): 281-91.
[http://dx.doi.org/10.1007/s11011-017-9965-8] [PMID: 28161776]
[39]
Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 1991; 88(11): 4651-5.
[http://dx.doi.org/10.1073/pnas.88.11.4651] [PMID: 1675786]
[40]
Yeh CL, Hsu CS, Chen SC, Hou YC, Chiu WC, Yeh SL. Effect of arginine on cellular adhesion molecule expression and leukocyte transmigration in endothelial cells stimulated by biological fluid from surgical patients. Shock 2007; 28(1): 39-44.
[http://dx.doi.org/10.1097/shk.0b013e31802f0190] [PMID: 17483743]
[41]
Williams TJ, Hellewell PG. Endothelial cell biology. Adhesion molecules involved in the microvascular inflammatory response. Am Rev Respir Dis 1992; 146(5 Pt 2): S45-50.
[http://dx.doi.org/10.1164/ajrccm/146.5_Pt_2.S45] [PMID: 1443907]
[42]
Sato Y, Kazumata K, Nakatani E, Houkin K, Kanatani Y. Characteristics of moyamoya disease based on national registry data in Japan. Stroke 2019; 50(8): 1973-80.
[http://dx.doi.org/10.1161/STROKEAHA.119.024689] [PMID: 31234758]
[43]
Hoshino S, Tsuda E, Miyazaki A. Vasospastic angina and asymptomatic moyamoya disease in a 14-year-old girl. Pediatr Int (Roma) 2018; 60(3): 296-7.
[http://dx.doi.org/10.1111/ped.13499] [PMID: 29480584]
[44]
Miller D, Waters DD, Warnica W, Szlachcic J, Kreeft J, Théroux P. Is variant angina the coronary manifestation of a generalized vasospastic disorder? N Engl J Med 1981; 304(13): 763-6.
[http://dx.doi.org/10.1056/NEJM198103263041306] [PMID: 7464885]
[45]
Choi W, Kim YN, Kim KH. Variant angina in moyamoya disease--a correlative etiology and different presentation: a case report. J Med Case Reports 2015; 9: 86.
[http://dx.doi.org/10.1186/s13256-015-0537-4] [PMID: 25895677]
[46]
Komiyama M, Nishikawa M, Yasui T, Otsuka M, Haze K. Moyamoya disease and coronary artery disease--case report. Neurol Med Chir (Tokyo) 2001; 41(1): 37-41.
[http://dx.doi.org/10.2176/nmc.41.37] [PMID: 11218639]
[47]
Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res 2015; 116(6): 960-75.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.303587] [PMID: 25767283]
[48]
Lee MY, Lai WT. Low plasma renin level is associated with the occurrence of angiographic radial artery spasm in patients undergoing transradial coronary procedures. Int J Cardiol 2014; 176(3): 1195-7.
[http://dx.doi.org/10.1016/j.ijcard.2014.07.232] [PMID: 25125018]
[49]
Research committee on the pathology and treatment of spontaneous occlusion of the Circle of Willis, health labour sciences research grant for research on measures for infractable diseases. Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the Circle of Willis). Neurol Med Chir (Tokyo) 2012; 52: 245-66.
[http://dx.doi.org/10.2176/nmc.52.245]
[50]
Oki K, Katsumata M, Izawa Y, Takahashi S, Suzuki N, Houkin K. Research committee on spontaneous occlusion of Circle of Willis (moyamoya disease). Trends of antiplatelet therapy for the management of moyamoya disease in Japan: results of a nationwide survey. J Stroke Cerebrovasc Dis 2018; 27(12): 3605-12.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.08.030] [PMID: 30220629]

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