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 4th; John A Curci; Nancy J Cox; Vivian Gama; Antentor Hinton Jr; Jose A Gomez

doi:10.1016/j.isci.2024.110436

SOX6 expression and aneurysms of the thoracic and abdominal aorta

iScience. 2024 Jul 24;27(9):110436. doi: 10.1016/j.isci.2024.110436. eCollection 2024 Sep 20.

Authors

David Carmona-Berrio^{1

2}, Isabel Adarve-Rengifo^{1

2}, Andrea G Marshall³, Zer Vue³, Duane D Hall⁴, Tyne W Miller-Fleming⁵, Ky'Era V Actkins⁵, Heather K Beasley³, Paula M Almonacid⁶, Pierina Barturen-Larrea^{1

2}, Quinn S Wells⁷, Marcos G Lopez⁸, Edgar Garza-Lopez⁹, Dao-Fu Dai¹⁰, Jianqiang Shao¹¹, Kit Neikirk³, Frederic T Billings 4th⁸, John A Curci¹², Nancy J Cox⁵, Vivian Gama^{1

2}, Antentor Hinton Jr³, Jose A Gomez¹³

Affiliations

¹ Vanderbilt University, Cell and Developmental Biology, Nashville, TN 37232, USA.
² Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
³ Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
⁴ Department of Internal Medicine, Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
⁵ Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
⁶ Department of Economics, EAFIT University, Medellín, Antioquia, Columbia.
⁷ Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
⁸ Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
⁹ Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
¹⁰ Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
¹¹ Central Microscopy Research Facility, University of Iowa, Iowa City, IA 52242, USA.
¹² Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
¹³ Department of Medicine / Clinical Pharmacology Division. Vanderbilt University Medical Center, Nashville, TN 37232, USA.

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.

Keywords: Cardiovascular medicine; Medical science; Molecular Genetics.