Abstract 043: Endovascular Biopsy and Genetic Profiling of Endothelial Cells in Intracranial and Extracranial Steno‐occlusive Disease: A Systematic Review
Authors: Richter K. , King P. , Masters M. , Bounajem M. , Budohowski K. , Grandhi R. 
Published: January 2025

Introduction

Ischemic stroke from intracranial and extracranial stenooclusive disease is the second leading cause of death worldwide. Studies have demonstrated the critical role of endothelial cells (EC) in the pathogenesis of atherosclerosis. Feasibility of endovascular biopsy for the evaluation of EC involved in intracranial and extracranial pathologies has been established. However, the genetic and transcriptomic analysis of exclusively EC involved in this disease has yet to be performed. We present a systematic review of all endovascular endothelial biopsies performed to date as well as a comprehensive review of the various endothelial cell genes involved in intracranial and extracranial stenooclusive disease, and their specific function.

Methods

PubMed, Embase, Scopus, Web of Science, and MEDLINE databases were queried from inception to July 2024; PRISMA guidelines were followed. Inclusion criteria consisted of intracranial or extracranial atherosclerosis, endothelial cell biopsy; transcriptomic analysis or genetic analysis. Exclusion criteria consisted of studies without primary data (e.g., reviews, editorials, commentaries), non‐human studies (excluded for the genomic/transcriptomic review, not endovascular biopsy review), or studies not involving genomic or transcriptomic analysis. Two independent reviewers (MS and PK) screened the titles and abstracts of all retrieved records, with discrepancies resolved through consultation with a third reviewer (KRR).

Results

A total of 313 studies were identified from PubMed (188), Scopus (48), Web of Science (30), Embase (24), and MEDLINE (23). 53 duplicate references were removed and 237 studies were excluded. Ultimately, 23 studies were included in the review. For endovascular biopsy, feasibility testing was established in pigs with detachable coils (89.0 ± 101.6 EC per coil), and rabbits, with coils and intracranial stents (7.93 ±8.33 EC per coil, 831.33 ± 887.73 EC per stent). For extracranial EC, 50 genes were highlighted with their various functions described, including collagen degradation, inflammation, cell adhesion, angiogenesis, etc. All cells were obtained from carotid endarterectomy specimens. The average number of endothelial cells collected was 1,771. The most frequent method of EC gene analysis was single cell RNA sequencing (scRNA‐seq) (61.2%). For intracranial EC, 29 genes were highlighted with their various functions described, including the promotion of arterial inflammation, leukocyte adhesion, blood clot formation, etc. Specimens were collected from various intracranial pathologies, the most common being intracranial aneurysms (28.3%). The most common method for EC collection was aneurysm coils (44.8%). The average number of EC collected was 98 cells. The most common method of EC gene analysis was Fluorescence‐activated cell sorting (FACS) with scRNA‐seq (44.7%).

Conclusion

ECs play a significant role in the pathogenesis of intracranial and extracranial stenooclusive disease through complex genetic and transcriptomic pathways. Precise identification of these various genes, and their specific functions, is vital to the discovery of novel therapeutic interventions. While feasibility of endothelial biopsy has been established and performed for a variety of intracranial pathologies, it has yet to be performed exclusively for intracranial or extracranial stenooclusive disease. Future studies should aim to overcome this limitation by performing endothelial biopsy of intracranial and extracranial stenooclusive disease, to more accurately characterize these complex biological processes.