iScience (Sep 2024)
SOX6 expression and aneurysms of the thoracic and abdominal aorta
- David Carmona-Berrio,
- Isabel Adarve-Rengifo,
- Andrea G. Marshall,
- Zer Vue,
- Duane D. Hall,
- Tyne W. Miller-Fleming,
- Ky’Era V. Actkins,
- Heather K. Beasley,
- Paula M. Almonacid,
- Pierina Barturen-Larrea,
- Quinn S. Wells,
- Marcos G. Lopez,
- Edgar Garza-Lopez,
- Dao-Fu Dai,
- Jianqiang Shao,
- Kit Neikirk,
- Frederic T. Billings, IV,
- John A. Curci,
- Nancy J. Cox,
- Vivian Gama,
- Antentor Hinton, Jr.,
- Jose A. Gomez
Affiliations
- David Carmona-Berrio
- Vanderbilt University, Cell and Developmental Biology, Nashville, TN 37232, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Isabel Adarve-Rengifo
- Vanderbilt University, Cell and Developmental Biology, Nashville, TN 37232, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Andrea G. Marshall
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
- Zer Vue
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
- Duane D. Hall
- Department of Internal Medicine, Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
- Tyne W. Miller-Fleming
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Ky’Era V. Actkins
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Heather K. Beasley
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
- Paula M. Almonacid
- Department of Economics, EAFIT University, Medellín, Antioquia, Columbia
- Pierina Barturen-Larrea
- Vanderbilt University, Cell and Developmental Biology, Nashville, TN 37232, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Quinn S. Wells
- Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Marcos G. Lopez
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Edgar Garza-Lopez
- Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
- Dao-Fu Dai
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
- Jianqiang Shao
- Central Microscopy Research Facility, University of Iowa, Iowa City, IA 52242, USA
- Kit Neikirk
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
- Frederic T. Billings, IV
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- John A. Curci
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
- Nancy J. Cox
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Vivian Gama
- Vanderbilt University, Cell and Developmental Biology, Nashville, TN 37232, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Antentor Hinton, Jr.
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA; Corresponding author
- Jose A. Gomez
- Department of Medicine / Clinical Pharmacology Division. Vanderbilt University Medical Center, Nashville, TN 37232, USA; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 9
p. 110436
Abstract
Summary: 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.
