Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly...

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Autores principales:	Kazim H. Narsinh, Kamileh Narsinh, David B. McCoy, Zhengda Sun, Cathra Halabi, Karl Meisel, Tarik Tihan, Krishna Chaganti, Matthew R. Amans, Van V. Halbach, Randall T. Higashida, Steven W. Hetts, Christopher F. Dowd, Ethan A. Winkler, Adib A. Abla, Tomasz J. Nowakowski, Daniel L. Cooke
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	fusiform aneurysm gene expression profile single cell RNA sequencing (scRNA-seq) polyarteritis nodosa (PAN) endovascular biopsy Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/5cefd84df9e64befbc1fad83ae8d2ca2
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spelling	oai:doaj.org-article:5cefd84df9e64befbc1fad83ae8d2ca22021-11-30T14:37:30ZEndovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa1664-229510.3389/fneur.2021.697105https://doaj.org/article/5cefd84df9e64befbc1fad83ae8d2ca22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.697105/fullhttps://doaj.org/toc/1664-2295Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa.Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis.Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα.Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.Kazim H. NarsinhKamileh NarsinhDavid B. McCoyZhengda SunCathra HalabiCathra HalabiKarl MeiselTarik TihanKrishna ChagantiMatthew R. AmansVan V. HalbachRandall T. HigashidaSteven W. HettsChristopher F. DowdEthan A. WinklerAdib A. AblaTomasz J. NowakowskiDaniel L. CookeFrontiers Media S.A.articlefusiform aneurysmgene expression profilesingle cell RNA sequencing (scRNA-seq)polyarteritis nodosa (PAN)endovascular biopsyNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fusiform aneurysm gene expression profile single cell RNA sequencing (scRNA-seq) polyarteritis nodosa (PAN) endovascular biopsy Neurology. Diseases of the nervous system RC346-429
spellingShingle	fusiform aneurysm gene expression profile single cell RNA sequencing (scRNA-seq) polyarteritis nodosa (PAN) endovascular biopsy Neurology. Diseases of the nervous system RC346-429 Kazim H. Narsinh Kamileh Narsinh David B. McCoy Zhengda Sun Cathra Halabi Cathra Halabi Karl Meisel Tarik Tihan Krishna Chaganti Matthew R. Amans Van V. Halbach Randall T. Higashida Steven W. Hetts Christopher F. Dowd Ethan A. Winkler Adib A. Abla Tomasz J. Nowakowski Daniel L. Cooke Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa
description	Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa.Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis.Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα.Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.
format	article
author	Kazim H. Narsinh Kamileh Narsinh David B. McCoy Zhengda Sun Cathra Halabi Cathra Halabi Karl Meisel Tarik Tihan Krishna Chaganti Matthew R. Amans Van V. Halbach Randall T. Higashida Steven W. Hetts Christopher F. Dowd Ethan A. Winkler Adib A. Abla Tomasz J. Nowakowski Daniel L. Cooke
author_facet	Kazim H. Narsinh Kamileh Narsinh David B. McCoy Zhengda Sun Cathra Halabi Cathra Halabi Karl Meisel Tarik Tihan Krishna Chaganti Matthew R. Amans Van V. Halbach Randall T. Higashida Steven W. Hetts Christopher F. Dowd Ethan A. Winkler Adib A. Abla Tomasz J. Nowakowski Daniel L. Cooke
author_sort	Kazim H. Narsinh
title	Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa
title_short	Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa
title_full	Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa
title_fullStr	Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa
title_full_unstemmed	Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa
title_sort	endovascular biopsy of vertebrobasilar aneurysm in patient with polyarteritis nodosa
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5cefd84df9e64befbc1fad83ae8d2ca2
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Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

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