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Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Authors :
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
Source :
Frontiers in Neurology, Vol 12 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

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.

Details

Language :
English
ISSN :
16642295
Volume :
12
Database :
Directory of Open Access Journals
Journal :
Frontiers in Neurology
Publication Type :
Academic Journal
Accession number :
edsdoj.5cefd84df9e64befbc1fad83ae8d2ca2
Document Type :
article
Full Text :
https://doi.org/10.3389/fneur.2021.697105