Intracranial Aneurysms: Pathology, Genetics, and Molecular Mechanisms

Xu, Zhen; Rui, Yanning; Hagan, John P.; Kim, Dong H.

doi:10.1007/s12017-019-08537-7

Cited by 85 publications

(60 citation statements)

References 180 publications

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“…There is no significant overlap in putative susceptibility genes between various ES-based studies [35], which may reflect a pronounced heterogeneity of IA/SAH pathogenesis. We also aimed to identify genetic risk factors for UIA/aSAH by a family-based ES approach, and we propose EDIL3 as new risk gene.…”

Section: Genetic and Functional Aspects On Edil3 As An Uia/ Asah Riskmentioning

confidence: 97%

Exome sequencing in 38 patients with intracranial aneurysms and subarachnoid hemorrhage

et al. 2020

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Objective Genetic risk factors for unruptured intracranial aneurysms (UIA) and aneurysmal subarachnoid hemorrhage (aSAH) are poorly understood. We aimed to verify recently reported risk genes and to identify novel sequence variants involved in the etiology of UIA/aSAH. Methods We performed exome sequencing (ES) in 35 unrelated individuals and 3 family members, each with a history of UIA and/or aSAH. We searched for sequence variants with minor allele frequency (MAF) ≤ 5% in the reported risk genes ADAMTS15, ANGPTL6, ARHGEF17, LOXL2, PCNT, RNF213, THSD1 and TMEM132B. To identify novel putative risk genes we looked for unknown (MAF = 0) variants shared by the three relatives. Results We identified 20 variants with MAF ≤ 5% in 18 individuals: 9 variants in PCNT (9 patients), 4 in RNF213 (3 patients), 3 in THSD1 (6 patients), 2 in ANGPTL6 (3 patients), 1 in ADAMTS15 (1 patient) and 1 in TMEM132B (1 patient). In the affected family, prioritization of shared sequence variants yielded five novel putative risk genes. Based on predicted pathogenicity of identified variants, population genetics data and a high functional relevance for vascular biology, EDIL3 was selected as top candidate and screened in additional 37 individuals with UIA and/or aSAH: a further very rare EDIL3 sequence variant in two unrelated sporadic patients was identified. Conclusions Our data support a role of sequence variants in PCNT, RNF213 and THSD1 as susceptibility factors for cerebrovascular disease. The documented function in vascular wall integrity, the crucial localization of affected amino acids and gene/variant association tests suggest EDIL3 as a further valid candidate disease gene for UIA/aSAH.

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Section: Genetic and Functional Aspects On Edil3 As An Uia/ Asah Riskmentioning

confidence: 97%

Exome sequencing in 38 patients with intracranial aneurysms and subarachnoid hemorrhage

et al. 2020

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“…Intracranial aneurysm is local dilatation in cerebral arteries, and about 2–5% cases can develop to rupture ( Xu et al, 2019 ). Smooth muscle cells are one key cell type-forming media in intracranial arteries and have significant roles in intracranial aneurysm formation and rupture ( Starke et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

CircRNA DOCK1 Regulates miR-409-3p/MCL1 Axis to Modulate Proliferation and Apoptosis of Human Brain Vascular Smooth Muscle Cells

Ding

Wang

Han

et al. 2021

Front. Cell Dev. Biol.

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BackgroundIntracranial aneurysm is an abnormal expansion in the intracranial arteries, which is associated with growth and apoptosis of vascular smooth muscle cells. Circular RNAs (circRNAs) have implicated in the progression of intracranial aneurysms. The purpose of this paper is to study the function and mechanism of circRNA dedicator of cytokinesis 1 (circ_DOCK1) in regulating proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs).MethodsHBVSMCs were exposed to hydrogen peroxide (H2O2). Cell proliferation and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and flow cytometry, respectively. Circ_DOCK1, microRNA (miR)-409-3p, and myeloid cell leukemia sequence 1 (MCL1) levels were examined by quantitative reverse transcription polymerase chain reaction or western blotting. The target association was assessed by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays.ResultsExposure to H2O2 decreased proliferation and increased apoptosis of HBVSMCs. Circ_DOCK1 expression was reduced in H2O2-treated HBVSMCs. Circ_DOCK1 overexpression rescued H2O2-caused reduction of proliferation and PCNA expression and attenuated H2O2-induced apoptosis and expression of Bcl-2, Bax, and cleaved PARP. MiR-409-3p was targeted by circ_DOCK1 and upregulated in H2O2-treated HBVSMCs. MiR-409-3p upregulation mitigated the role of circ_DOCK1 in proliferation and apoptosis of H2O2-treated HBVSMCs. MCL1 was targeted via miR-409-3p and downregulated via H2O2 treatment. Circ_DOCK1 overexpression enhanced MCL1 expression via modulating miR-409-3p. MiR-409-3p knockdown weakened H2O2-induced proliferation reduction and apoptosis promotion via regulating MCL1.ConclusionCirc_DOCK1 overexpression mitigated H2O2-caused proliferation inhibition and apoptosis promotion in HBVSMCs by modulating miR-409-3p/MCL1 axis.

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“…Disamping itu, sekitar 7-20%, diketahui bahwa pasien yang memiliki riwayat keluarga, dan kerabat dekat berisiko lebih tinggi, terlepas dari latar belakang etnisnya. 6 Aneurisma karotis kavernosa (AKK) merupakan suatu penyebab patologi yang tidak umum karena letak aneurisma pada ruang ekstradural. Apabila ukuran aneurismanya kecil maka tidak akan berisiko terjadinya perdarahan subaraknoid, namun apabila ukurannya besar akan menimbulkan tanda dan gejala berupa efek penekanan massa.…”

Section: Pembahasanunclassified

Terapi Endovaskular Aneurisma Karotis Kavernosa Dengan Pipeline Flex Embolization Device: Pengamatan 1 Tahun

Amran

Ban²,

Bahar³

et al. 2020

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ENDOVASCULAR TREATMENT CAVERNOUS CAROTID ANEURYSM WITH PIPELINE FLEX EMBOLIZATION DEVICE: 1-YEAR FOLLOW UPABSTRACTAsymptomatic intracranial aneurysms are usually detected accidentally through neuroimaging. However, a large intracranial aneurysm (15-24mm) is more likely to manifest clinically due to its mass effect. Aneurysms in the cavernous segment of carotid artery generally exhibit occulomotor nerve palsy, headache and dizziness. The selection of endovascular therapy depends on the type and morphology of the aneurysm. Currently, the treatment options were stent-assisted coil and pipeline embolization device (PED). We reported two cases of large symptomatic unruptured cavernous carotid aneurysm (CCA), treated with the flow diverter technique using a pipeline flex embolization device (PED flex) the second generation of PED. The first case was a 59-year-old woman with complaint of diplopia and headache. Computed Tomography (CT) angiography and 3 dimensional (D) brain imaging revealed bilateral aneurysms, one was in the right cavernous carotid (16.1x16.6mm) and the other was in the left cavernous carotid (9.2x6.5mm). In second case a 67-year-old woman with complaint of headache. Magnetic resonance angiography (MRA) revealed a 15mm aneurysm in the right cavernous carotid. Both aneurysms were treated using PED flex (4.75mm diameter/25mm length and 4mm diameter/25mm length, respectively), except the left cavernous carotid aneurysm in the first case. Six month and one year follow up angiograms were obtained, and showed complete occlusion of aneurysms. Flow diverter technique using PED flex is a feasible and effective treatment for large symptomatic unruptured carotid cavernous aneurysms.Keywords: Embolization, flow-diverter, large cavernous carotid aneurysms, pipeline flex embolization device (PED flex)ABSTRAKAneurisma intrakranial asimptomatik biasanya terdeteksi secara tidak sengaja melalui pemeriksaan pencitraan neuroradiologis. Akan tetapi aneurisma intrakranial yang besar (15-24mm) cenderung memberikan gejala klinis akibat efek massa yang ditimbulkan. Apabila aneurisma terletak di arteri karotis segmen kavernosa, penderita dapat mengalami paresis nervus okulomotor dan juga terkadang memberikan gejala nyeri kepala serta rasa pusing. Pemilihan terapi endovaskuler bergantung pada tipe dan morfologi dari aneurisma. Saat ini, pemilihan terapi endovaskuler dapat berupa stent-assisted coiling dan alat embolisasi pipeline. Kami melaporkan dua kasus aneurisma karotis kavernosa (AKK) tidak pecah berukuran besar simptomatik dengan teknik flow-diverter menggunakan pipeline flex embolization device (PED flex) yang merupakan generasi kedua dari alat embolisasi pipeline. Pada kasus pertama wanita 59 tahun dengan keluhan diplopia dan nyeri kepala, pemeriksaan Computed Tomography (CT) angiografi dan 3 dimensi (D) otak ditemukan aneurisma pada karotis kavernosa bilateral, yang masing-masing berukuran (16,1x16,6mm) pada sisi kanan dan (9,2x6,5mm) pada sisi kiri. Pada kasus kedua, wanita 67 tahun dengan keluhan nyeri kepala. Pemeriksaan MRA otak ditemukan aneurisma berukuran 15mm pada karotis kavernosa sebelah kanan. Masing-masing aneurisma diterapi dengan PED flex (4,75mm diameter/25mm panjang dan 4mm diameter/25mm panjang), kecuali aneurisma pada karotis kavernosa sebelah kiri pada kasus pertama. Follow-up pada enam bulan dan satu tahun kemudian, dengan pemeriksaan angiografi, menunjukkan oklusi komplet pada masing- masing aneurisma. Terapi endovaskular dengan teknik flow-diverter menggunakan PED flex merupakan modalitas terapi yang efektif dan dapat dilaksanakan untuk aneurisma karotis kavernosa berukuran besar bergejala.Kata kunci: Aneurisma karotis kavernosa besar, embolisasi, flow-diverter, pipeline flex embolization device (PED flex)

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Intracranial Aneurysms: Pathology, Genetics, and Molecular Mechanisms

Cited by 85 publications

References 180 publications

Exome sequencing in 38 patients with intracranial aneurysms and subarachnoid hemorrhage

Exome sequencing in 38 patients with intracranial aneurysms and subarachnoid hemorrhage

CircRNA DOCK1 Regulates miR-409-3p/MCL1 Axis to Modulate Proliferation and Apoptosis of Human Brain Vascular Smooth Muscle Cells

Terapi Endovaskular Aneurisma Karotis Kavernosa Dengan Pipeline Flex Embolization Device: Pengamatan 1 Tahun

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