Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms
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-as...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Diagnostics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4418/11/8/1442 |
| _version_ | 1797524196213915648 |
|---|---|
| author | Vincent M. Tutino Yongjun Lu Daizo Ishii Kerry E. Poppenberg Hamidreza Rajabzadeh-Oghaz Adnan H. Siddiqui David M. Hasan |
| author_facet | Vincent M. Tutino Yongjun Lu Daizo Ishii Kerry E. Poppenberg Hamidreza Rajabzadeh-Oghaz Adnan H. Siddiqui David M. Hasan |
| author_sort | Vincent M. Tutino |
| collection | DOAJ |
| description | 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 (<i>CBWD6</i>, <i>MT2A</i>, <i>MZT2B</i>, <i>PIM3</i>, <i>SLC37A3</i>, and <i>TNFRSF4</i>) was significantly higher in intraluminal blood, while the expression of 3/18 genes (<i>ST6GALNAC1</i>, <i>TCN2</i>, and <i>UFSP1</i>) was significantly lower. There was a significant, positive correlation between intraluminal and proximal expression of <i>CXCL10</i>, <i>MT2A</i>, and <i>MZT2B</i>, suggesting local increases of these genes is reflected in the periphery. Expression of <i>ST6GALNAC1</i> and <i>TIFAB</i> was significantly positively correlated with IA size, while expression of <i>CCDC85B</i> 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. |
| first_indexed | 2024-03-10T08:53:57Z |
| format | Article |
| id | doaj.art-ca56413ba42148f29514f4001f7f997f |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T08:53:57Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-ca56413ba42148f29514f4001f7f997f2023-11-22T07:20:34ZengMDPI AGDiagnostics2075-44182021-08-01118144210.3390/diagnostics11081442Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial AneurysmsVincent M. Tutino0Yongjun Lu1Daizo Ishii2Kerry E. Poppenberg3Hamidreza Rajabzadeh-Oghaz4Adnan H. Siddiqui5David M. Hasan6Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY 14260, USADepartment of Cardiovascular Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USADepartment of Neurosurgery, University of Iowa Hospitals and Clinics, 1616 JCP, 200 Hawkins Dr, Iowa City, IA 52242, USACanon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY 14260, USACanon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY 14260, USACanon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY 14260, USADepartment of Neurosurgery, University of Iowa Hospitals and Clinics, 1616 JCP, 200 Hawkins Dr, Iowa City, IA 52242, USAThe 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 (<i>CBWD6</i>, <i>MT2A</i>, <i>MZT2B</i>, <i>PIM3</i>, <i>SLC37A3</i>, and <i>TNFRSF4</i>) was significantly higher in intraluminal blood, while the expression of 3/18 genes (<i>ST6GALNAC1</i>, <i>TCN2</i>, and <i>UFSP1</i>) was significantly lower. There was a significant, positive correlation between intraluminal and proximal expression of <i>CXCL10</i>, <i>MT2A</i>, and <i>MZT2B</i>, suggesting local increases of these genes is reflected in the periphery. Expression of <i>ST6GALNAC1</i> and <i>TIFAB</i> was significantly positively correlated with IA size, while expression of <i>CCDC85B</i> 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.https://www.mdpi.com/2075-4418/11/8/1442cerebral aneurysmbiomarkersgene expressiontranscriptomicswhole blood |
| spellingShingle | Vincent M. Tutino Yongjun Lu Daizo Ishii Kerry E. Poppenberg Hamidreza Rajabzadeh-Oghaz Adnan H. Siddiqui David M. Hasan Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms Diagnostics cerebral aneurysm biomarkers gene expression transcriptomics whole blood |
| title | Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms |
| title_full | Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms |
| title_fullStr | Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms |
| title_full_unstemmed | Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms |
| title_short | Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms |
| title_sort | aberrant whole blood gene expression in the lumen of human intracranial aneurysms |
| topic | cerebral aneurysm biomarkers gene expression transcriptomics whole blood |
| url | https://www.mdpi.com/2075-4418/11/8/1442 |
| work_keys_str_mv | AT vincentmtutino aberrantwholebloodgeneexpressioninthelumenofhumanintracranialaneurysms AT yongjunlu aberrantwholebloodgeneexpressioninthelumenofhumanintracranialaneurysms AT daizoishii aberrantwholebloodgeneexpressioninthelumenofhumanintracranialaneurysms AT kerryepoppenberg aberrantwholebloodgeneexpressioninthelumenofhumanintracranialaneurysms AT hamidrezarajabzadehoghaz aberrantwholebloodgeneexpressioninthelumenofhumanintracranialaneurysms AT adnanhsiddiqui aberrantwholebloodgeneexpressioninthelumenofhumanintracranialaneurysms AT davidmhasan aberrantwholebloodgeneexpressioninthelumenofhumanintracranialaneurysms |