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

Diagnostics

Kerry E. Poppenberg¹  Hamidreza Rajabzadeh-Oghaz¹  Adnan H. Siddiqui¹  Vincent M. Tutino¹  Yongjun Lu²  Daizo Ishii³  David M. Hasan³ 

[1] Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY 14260, USA;Department of Cardiovascular Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA;Department of Neurosurgery, University of Iowa Hospitals and Clinics, 1616 JCP, 200 Hawkins Dr, Iowa City, IA 52242, USA;

关键词: cerebral aneurysm;    biomarkers;    gene expression;    transcriptomics;    whole blood;   

DOI  :  10.3390/diagnostics11081442

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown