Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms

Vincent M. Tutino; Yongjun Lu; Daizo Ishii; Kerry E. Poppenberg; Hamidreza Rajabzadeh-Oghaz; Adnan H. Siddiqui; David M. Hasan

doi:10.3390/diagnostics11081442

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Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms

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Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms

Vincent M. Tutino, Yongjun Lu, Daizo Ishii, Kerry E. Poppenberg, Hamidreza Rajabzadeh-Oghaz, Adnan H. Siddiqui and David M. Hasan

Diagnostics (Basel), Vol.11(8), p.1442

08/10/2021

DOI: 10.3390/diagnostics11081442

PMCID: PMC8392298

PMID: 34441376

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Abstract

The rupture of an intracranial aneurysm (IA) causes devastating hemorrhagic strokes. Yet, most IAs remain asymptomatic and undetected until they rupture. In the search for circulating biomarkers of unruptured IAs, we previously performed transcriptome profiling on whole blood and identified an IA-associated panel of 18 genes. In this study, we seek to determine if these genes are also differentially expressed within the IA lumen, which could provide a mechanistic link between the disease and the observed circulating gene expression patterns. To this end, we collected blood from the lumen of 37 IAs and their proximal parent vessels in 31 patients. The expression levels of 18 genes in the lumen and proximal vessel were then measured by quantitative polymerase chain reaction. This analysis revealed that the expression of 6/18 genes (CBWD6, MT2A, MZT2B, PIM3, SLC37A3, and TNFRSF4) was significantly higher in intraluminal blood, while the expression of 3/18 genes (ST6GALNAC1, TCN2, and UFSP1) was significantly lower. There was a significant, positive correlation between intraluminal and proximal expression of CXCL10, MT2A, and MZT2B, suggesting local increases of these genes is reflected in the periphery. Expression of ST6GALNAC1 and TIFAB was significantly positively correlated with IA size, while expression of CCDC85B was significantly positively correlated with IA enhancement on post-contrast MRI, a metric of IA instability and risk. In conclusion, intraluminal expression differences in half of the IA-associated genes observed in this study provide evidence for IA tissue-mediated transcriptional changes in whole blood. Additionally, some genes may be informative in assessing IA risk, as their intraluminal expression was correlated to IA size and aneurysmal wall enhancement.

General & Internal Medicine

Life Sciences & Biomedicine

Medicine, General & Internal

Science & Technology

Details

Title: Subtitle: Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms
Creators: Vincent M. Tutino - University at Buffalo, State University of New York
Yongjun Lu - University of Iowa Hospitals and Clinics
Daizo Ishii - University of Iowa Hospitals and Clinics
Kerry E. Poppenberg - University at Buffalo, State University of New York
Hamidreza Rajabzadeh-Oghaz - University at Buffalo, State University of New York
Adnan H. Siddiqui - University at Buffalo, State University of New York
David M. Hasan - University of Iowa Hospitals and Clinics
Resource Type: Journal article
Publication Details: Diagnostics (Basel), Vol.11(8), p.1442
DOI: 10.3390/diagnostics11081442
PMID: 34441376
PMCID: PMC8392298
NLM abbreviation: Diagnostics (Basel)
ISSN: 2075-4418
eISSN: 2075-4418
Publisher: Mdpi
Number of pages: 12
Language: English
Date published: 08/10/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Critical Care; Stead Family Department of Pediatrics
Record Identifier: 9984419142802771

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