Angiopoietin-2 associates with poor prognosis in Moyamoya angiopathy.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
24 Apr 2024
24 Apr 2024
Historique:
revised:
04
03
2024
received:
28
12
2023
accepted:
09
04
2024
medline:
24
4
2024
pubmed:
24
4
2024
entrez:
24
4
2024
Statut:
aheadofprint
Résumé
Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterized by recurrent ischemic/hemorrhagic strokes due to progressive occlusion of the intracranial carotid arteries. The lack of reliable disease severity biomarkers led us to investigate molecular features of a Caucasian cohort of MA patients. The participants consisted of 30 MA patients and 40 controls. We measured cerebrospinal fluid (CSF) levels of angiogenic/inflammatory factors (ELISA). We then applied quantitative real-time PCR on cerebral artery specimens for expression analyses of angiogenic factors. By an immunoassay based on microfluidic technology, we examined the potential correlations between plasma protein expression and MA clinical progression. A RNA interference approach toward Ring Finger Protein 213 (RNF213) and a tube formation assay were applied in cellular model. We detected a statistically significant (p < 0.000001) up-regulation of Angiopoietin-2 (Ang-2) in CSF and stenotic middle cerebral arteries (RQ >2) of MA patients compared to controls. A high Ang-2 plasma concentration (p = 0.018) was associated with unfavorable outcome in a subset of MA patients. ROC curve analyses indicated Ang-2 as diagnostic CSF biomarker (>3741 pg/mL) and prognostic plasma biomarker (>1162 pg/mL), to distinguish stable-from-progressive MA. Consistently, MA cellular model showed a significant up-regulation (RQ >2) of Ang-2 in RNF213 silenced condition. Our results pointed out Ang-2 as a reliable biomarker mirroring arterial steno-occlusion and vascular instability of MA in CSF and blood, providing a candidate factor for patient stratification. This pilot study may pave the way to the validation of a biomarker to identify progressive MA patients deserving a specific treatment path.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Italian Ministry of Health
ID : RCR-2021-23671214
Organisme : Italian Ministry of Health
ID : RF-2019-12369247
Organisme : Italian Ministry of Health
ID : RRC 2018-2023
Informations de copyright
© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Fukui M. Guidelines for the diagnosis and treatment of spontaneous occlusion of the circle of Willis (‘Moyamoya’ disease). Research committee on spontaneous occlusion of the circle of Willis (Moyamoya disease) of the Ministry of Health and Welfare, Japan. Clin Neurol Neurosurg. 1997;99(Suppl 2):S238‐S240.
Guey S, Tournier‐Lasserve E, Hervé D, Kossorotoff M. Moyamoya disease and syndromes: from genetics to clinical management. Appl Clin Genet. 2015;8:49‐68. doi:10.2147/TACG.S4277
Kobayashi E, Saeki N, Oishi H, Hirai S, Yamaura A. Long‐term natural history of hemorrhagic Moyamoya disease in 42 patients. J Neurosurg. 2000;93(6):976‐980. doi:10.3171/jns.2000.93.6.0976
Bonasia S, Ciccio G, Smajda S, et al. Angiographic analysis of natural anastomoses between the posterior and anterior cerebral arteries in Moyamoya disease and syndrome. AJNR Am J Neuroradiol. 2019;40:2066‐2072. doi:10.3174/ajnr.A6291
Yu J, Zhang J, Chen J. The significance of leptomeningeal collaterals in Moyamoya disease. CNS Neurosci Ther. 2020;26:776. doi:10.1111/cns.13389
Fang YC, Wei LF, Hu CJ, Tu YK. Pathological circulating factors in Moyamoya disease. Int J Mol Sci. 2021;22(4):1696. doi:10.3390/ijms22041696
Miyamoto S, Yoshimoto T, Hashimoto N, et al. Effects of extracranial‐intracranial bypass for patients with hemorrhagic Moyamoya disease: results of the Japan adult Moyamoya trial. Stroke. 2014;45(5):1415‐1421. doi:10.1161/STROKEAHA.113.004386
Young AM, Karri SK, Ogilvy CS, Zhao N. Is there a role for treating inflammation in Moyamoya disease?: a review of histopathology, genetics, and signaling cascades. Front Neurol. 2013;4:105. doi:10.3389/fneur.2013.00105
Guey S, Kraemer M, Hervé D, et al. Rare RNF213 variants in the C‐terminal region encompassing the RING‐finger domain are associated with Moyamoya angiopathy in Caucasians. Eur J Hum Genet. 2017;25(8):995‐1003. doi:10.1038/ejhg.2017.92
Kamada F, Aoki Y, Narisawa A, et al. A genome‐wide association study identifies RNF213 as the first Moyamoya disease gene. J Hum Genet. 2011;56(1):34‐40. doi:10.1038/jhg.2010.132
Dorschel KB, Wanebo JE. Genetic and proteomic contributions to the pathophysiology of Moyamoya Angiopathy and related vascular diseases. Appl Clin Genet. 2021;14:145‐171. doi:10.2147/TACG.S252736
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(5):245‐266. doi:10.2176/nmc.52.245
Bersano A, Bedini G, Nava S, et al. GEN‐O‐MA project: an Italian network studying clinical course and pathogenic pathways of Moyamoya disease‐study protocol and preliminary results. Neurol Sci. 2019;40(3):561‐570. doi:10.1007/s10072‐018‐3664‐z
Bersano A, Khan N, Fuentes B, et al. European stroke organisation (ESO) guidelines on Moyamoya angiopathy endorsed by vascular European reference network (VASCERN). Eur Stroke J. 2023;8(1):55‐84. doi:10.1177/23969873221144089
Suzuki J, Takaku A. Cerebrovascular “Moyamoya” disease. Disease showing abnormal net‐like vessels in base of brain. Arch Neurol. 1969;20(3):288‐299. doi:10.1001/archneur.1969.00480090076012
Tinelli F, Nava S, Arioli F, et al. Vascular remodeling in Moyamoya Angiopathy: from peripheral blood mononuclear cells to endothelial cells. Int J Mol Sci. 2020;21(16):5763. doi:10.3390/ijms21165763
Cao J, Seegmiller J, Hanson NQ, Zaun C, Li D. A microfluidic multiplex proteomic immunoassay device for translational research. Clin Proteomics. 2015;12:28. doi:10.1186/s12014‐015‐9101‐x
Aldo P, Marusov G, Svancara D, David J, Mor G. Simple Plex(™): a novel multi‐Analyte, automated microfluidic immunoassay platform for the detection of human and mouse cytokines and chemokines. Am J Reprod Immunol. 2016;75(6):678‐693. doi:10.1111/aji.12512
Dei Cas M, Carrozzini T, Pollaci G, et al. Plasma lipid profiling contributes to untangle the complexity of Moyamoya Arteriopathy. Int J Mol Sci. 2021 Dec 14;22(24):13410. doi:10.3390/ijms222413410
Mamiya T, Kanamori F, Yokoyama K, et al. Long noncoding RNA profile of the intracranial artery in patients with Moyamoya disease. J Neurosurg. 2022;138(3):709‐716. doi:10.3171/2022.5.JNS22579
Xu S, Wei W, Zhang F, et al. Transcriptomic profiling of intracranial arteries in adult patients with Moyamoya disease reveals novel insights into its pathogenesis. Front Mol Neurosci. 2022;15:881954. doi:10.3389/fnmol.2022.881954
Liu X, Jin F, Wang C, et al. Targeted metabolomics analysis of serum amino acid profiles in patients with Mo‐yamoya disease. Amino Acids. 2022;54(1):137‐146. doi:10.1007/s00726‐021‐03100‐w
Wang X, Han C, Jia Y, Wang J, Ge W, Duan L. Proteomic profiling of exosomes from hemorrhagic Moyamoya disease and dysfunction of mitochondria in endothelial cells. Stroke. 2021;52(10):3351‐3361. doi:10.1161/STROKEAHA.120.032297
He S, Zhang J, Liu Z, et al. Upregulated cytoskeletal proteins promote pathological angiogenesis in Moyamoya disease. Stroke. 2023;54(12):3153‐3164. doi:10.1161/STROKEAHA.123.044476
Canavero I, Vetrano IG, Zedde M, et al. Clinical Management of Moyamoya Patients. J Clin Med. 2021 Aug 17;10(16):3628. doi:10.3390/jcm10163628
Scholz A, Plate KH, Reiss Y. Angiopoietin‐2: a multifaceted cytokine that functions in both angiogenesis and inflammation. Ann N Y Acad Sci. 2015;1347:45‐51. doi:10.1111/nyas.12726
Coelho AL, Gomes MP, Catarino RJ, et al. Angiogenesis in NSCLC: is vessel co‐option the trunk that sustains the branches? Oncotarget. 2017;8(24):39795‐39804. doi:10.18632/oncotarget.7794
Felcht M, Luck R, Schering A, et al. Angiopoietin‐2 differentially regulates angiogenesis through TIE2 and integrin signaling. J Clin Invest. 2012;122(6):1991‐2005. doi:10.1172/JCI58832
Hakanpaa L, Sipila T, Leppanen VM, et al. Endothelial destabilization by angiopoietin‐2 via integrin β1 activation. Nat Commun. 2015;6:5962. doi:10.1038/ncomms6962
Saharinen P, Eklund L, Alitalo K. Therapeutic targeting of the angiopoietin‐TIE pathway. Nat Rev Drug Discov. 2017;16(9):635‐661. doi:10.1038/nrd.2016.278
Nagai N, Lundh von Leithner P, Izumi‐Nagai K, et al. Spontaneous CNV in a novel mutant mouse is associated with early VEGF‐A‐driven angiogenesis and late‐stage focal edema, neural cell loss, and dysfunction. Invest Ophthalmol Vis Sci. 2014 May 20;55(6):3709‐3719. doi:10.1167/iovs.14‐13989
Rossato FA, Su Y, Mackey A, Ng YSE. Fibrotic changes and endothelial‐to‐mesenchymal transition promoted by VEGFR2 antagonism alter the therapeutic effects of VEGFA pathway blockage in a mouse model of choroidal neovascularization. Cells. 2020;9(9):2057. doi:10.3390/cells9092057
Scott RM, Smith ER. Moyamoya disease and Moyamoya syndrome. N Engl J Med. 2009;360(12):1226‐1237. doi:10.1056/NEJMra0804622
Wollborn J, Zhang Z, Gaa J, et al. Angiopoietin‐2 is associated with capillary leak and predicts complications after cardiac surgery. Ann Intensive Care. 2023;13(1):70. doi:10.1186/s13613‐023‐01165‐2
Liu W, Morito D, Takashima S, et al. Identification of RNF213 as a susceptibility gene for Moyamoya disease and its possible role in vascular development. PLoS One. 2011;6(7):e22542. doi:10.1371/journal.pone.0022542
Canonica J, Foxton R, Garrido MG, et al. Delineating effects of angiopoietin‐2 inhibition on vascular permeability and inflammation in models of retinal neovascularization and ischemia/reperfusion. Front Cell Neurosci. 2023;17:1192464. doi:10.3389/fncel.2023.1192464
Chang FC, Chiang WC, Tsai MH, et al. Angiopoietin‐2‐induced arterial stiffness in CKD. J Am Soc Nephrol. 2014;25(6):1198‐1209. doi:10.1681/ASN.2013050542
Chang FC, Liu CH, Luo AJ, et al. Angiopoietin‐2 inhibition attenuates kidney fibrosis by hindering chemokine C‐C motif ligand 2 expression and apoptosis of endothelial cells. Kidney Int. 2022;102(4):780‐797. doi:10.1016/j.kint.2022.06.026