Journal article
SOX6 expression and aneurysms of the thoracic and abdominal aorta
iScience, Vol.27(9), 110436
07/2024
DOI: 10.1016/j.isci.2024.110436
PMCID: PMC11388018
PMID: 39262802
Abstract
Abdominal and thoracic aortic aneurysms (AAAs, TAAs) remain a major cause of deaths worldwide, in part due to the lack of reliable prognostic markers or early warning signs. Sox6 has been found to regulate renin controlling blood pressure. We hypothesized that Sox6 may serve as an important regulator of the mechanisms contributing to hypertension-induced aortic aneurysms. Phenotype and laboratory-wide association scans in a clinical cohort found that SOX6 gene expression is associated with aortic aneurysm in subjects of European ancestry. Sox6 and tumor necrosis factor alpha (TNF-α) expression were upregulated in aortic tissues from patients affected by either AAA or TAA. In Sox6 knockout mice with angiotensin-II-induced AAA, we found that Sox6 plays critical role in the development and progression of AAA. Our data support a regulatory role of SOX6 in the development of hypertension-induced AAA, suggesting that Sox6 may be a therapeutic target for the treatment of aortic aneurysms.
[Display omitted]
•Using electronic health records and biobank samples, we found that the transcription factor SOX6 is associated with abdominal and thoracic aortic aneurysm and its expression is upregulated in tissue from patients affected by those diseases•Laboratory-wide association study (LabWAS) provides several clinical laboratory measurements associated with aortic aneurysm diagnosis that may be potential biomarkers for the disease•Knocking out Sox6 from the smooth muscle cells of mice attenuated hypertension-induced abdominal aortic aneurysm. These transgenic mice may be useful tools to elucidate the mechanisms associated with abdominal aortic aneurysm
Medical science; Cardiovascular medicine; Molecular Genetics
Details
- Title: Subtitle
- SOX6 expression and aneurysms of the thoracic and abdominal aorta
- Creators
- David Carmona-Berrio - Vanderbilt UniversityIsabel Adarve-Rengifo - Vanderbilt UniversityAndrea G. Marshall - Vanderbilt UniversityZer Vue - Vanderbilt UniversityDuane D. Hall - University of IowaTyne W. Miller-Fleming - Vanderbilt University Medical CenterKy’Era V. Actkins - Vanderbilt University Medical CenterHeather K. Beasley - Vanderbilt UniversityPaula M. Almonacid - Universidad EAFITPierina Barturen-Larrea - Vanderbilt UniversityQuinn S. Wells - Vanderbilt University Medical CenterMarcos G. Lopez - Vanderbilt University Medical CenterEdgar Garza-Lopez - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USADao-Fu Dai - University of IowaJianqiang Shao - Central Microscopy Research Facility, University of Iowa, Iowa City, IA 52242, USAKit Neikirk - Vanderbilt UniversityFrederic T. Billings - Vanderbilt University Medical CenterJohn A. Curci - Vanderbilt University School of MedicineNancy J. Cox - Vanderbilt University Medical CenterVivian Gama - Vanderbilt UniversityAntentor Hinton - Vanderbilt UniversityJose A. Gomez - Vanderbilt University Medical Center
- Resource Type
- Journal article
- Publication Details
- iScience, Vol.27(9), 110436
- DOI
- 10.1016/j.isci.2024.110436
- PMID
- 39262802
- PMCID
- PMC11388018
- NLM abbreviation
- iScience
- ISSN
- 2589-0042
- eISSN
- 2589-0042
- Publisher
- Elsevier Inc
- Grant note
- NHLBI Research Scientist Development Grant: 1K01HL135461-01 NHLBI: R25 HL105446
We want to thank Dr. Lea Davis for her technical assistance with the BioVU data set analysis. The Synthetic Derivative and BioVU projects at Vanderbilt University Medical Center are supported by numerous sources: institutional funding, private agencies, and federal grants, including the NIH-funded Shared Instrumentation grants S10OD017985 and S10RR025141 and CTSA grants UL1TR002243, UL1TR000445, and UL1RR024975 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Genomic data are also supported by investigator-led projects that include U01HG004798, R01NS032830, RC2GM092618, P50GM115305, U01HG006378, U19HL065962, and R01HD074711 and additional funding sources listed at https://victr.vumc.org/biovu-funding/. UNCF/BMS EE United Negro College Fund/Bristol-Myers Squibb E.E. Just Postgraduate Fellowship in the Life Sciences Fellowship to H.K.B., The United Negro College Fund/Bristol-Myers Squibb E.E. Just Faculty Fund, Burroughs Wellcome Fund Career Awards at the Scientific Interface Award, Burroughs Wellcome Fund Adhoc Award, National Institutes of Health Small Research Pilot Subaward to 5R25HL106365-12 from the National Institutes of Health PRIDE Program, DK020593, Vanderbilt Diabetes and Research Training Center for DRTC Alzheimer's DiseasePilot & Feasibility Program to A.H.J. Research was supported by NHLBI Research Scientist Development Grant (1K01HL135461-01) to J.A.G. Small Research Project (SRP) Subaward from PRIDE-CVD to J.A.G.; SRPs are funded by an NHLBI grant #R25 HL105446 to Dr. Mohamed Boutjdir.Pilot & Feasibility Program to A.H.J. Research was supported by NHLBI Research Scientist Development Grant (1K01HL135461-01) to J.A.G. Small Research Project (SRP) Subaward from PRIDE-CVD to J.A.G.; SRPs are funded by an NHLBI grant #R25 HL105446 to Dr. Mohamed Boutjdir.r Pilot & Feasibility Program to A.H.J. Research was supported by NHLBI Research Scientist Development Grant (1K01HL135461-01) to J.A.G. Small Research Project (SRP) Subaward from PRIDE-CVD to J.A.G.; SRPs are funded by an NHLBI grant #R25 HL105446 to Dr. Mohamed Boutjdir.
- Language
- English
- Electronic publication date
- 07/2024
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984693976902771
Metrics
7 Record Views