A model aorta (cross-section) stained with calponin (red) elastin (green) and cell nuclei (blue).

Research

Francesca Seta, PhD, and Jingyan Han, PhD, Awarded NIH Grant to Further Understanding of Aortic Aneurysms

Despite tremendous advances, targeted therapies are still critically lacking

Francesca Seta, PhD, associate professor of medicine at Boston University Chobanian and Avedisian School of Medicine, and Jingyan Han, PhD, assistant professor medicine, have received a multiple PI R01 grant from the National Institutes of Health’s National Heart, Lung, and Blood Institute. The four-year, $3.1M award will support the project, “Thiol redox signaling in aortic aneurysm.”

Seta studies the basic mechanisms of vascular diseases, with an emphasis on the biology of the vascular smooth muscle. Her current research seeks to understand the molecular mechanisms of arterial stiffening and aortic aneurysms/dissections, two degenerative vascular conditions for which there are no therapies. Aortic aneurysms are abnormal dilatations of the aorta, the largest artery in the body, which often remain clinically silent until the aortic wall dissects, potentially leading to death.

Han’s research involves the molecular mechanisms of atherosclerotic cardiovascular disease with a particular focus on the role of redox signaling (the cellular communication process involving the reversible oxidation and reduction of molecules) in vascular endothelial cell dysfunction in response to various risk factors including hyperlipidemia, aging and chronic alcohol abuse.

Their new study will examine whether oxidative post-translational modifications on the enzyme sirtuin-1 are associated with aortic wall degradation processes causing aortic aneurysm. They will test whether preventing sirtuin-1 oxidation prevents these redox signaling processes thereby preventing aortic aneurysms and dissections.

“Our innovative studies will fill knowledge gaps on redox mechanisms of thoracic aortic aneurysm and aortic dissection (TAAD) and pave the way for targeted therapies to prevent TAAD in individuals at risk, such as those with Marfan syndrome, for which currently there are very limited treatment options,” explains Seta.

“Targeting redox signaling in aortic aneurysm represents a completely new avenue for understanding disease mechanisms,” said Han. “Our research explores redox biology not just as a pathological consequence but as a potential therapeutic target—an emerging concept in redox medicine.”

Previously, Seta identified the transcription factor Bcl11b as a crucial regulator of vascular smooth muscle function, which is critical for arterial structural integrity. In addition, her ongoing projects focus on the role of the lysine deacetylase sirtuin-1, known as the “longevity” gene and a molecular target of caloric restriction, in vascular homeostasis. She demonstrated that sirtuin-1 genetic overexpression or pharmacological activation exerts beneficial anti-oxidant and anti-inflammatory effects in the aortic wall, protecting against obesity-induced arterial stiffness and cardiac diastolic dysfunction. On the opposite, lack of sirtuin-1 in vascular smooth muscle cause aortic dissection in mice treated with angiotensin II.

Han has developed a novel optical coherence tomography-based vascular imaging system enabling real-time measure 3D angiography and hemodynamics of femoral artery of experimental models in vivo, which is noninvasive, label-free, contact-free, and high degree of automation in data acquisition and processing.

Seta received her BSc/MSc from the Università degli Studi “G. d’Annunzio” Chieti-Pescara, Italy and her PhD from New York Medical College.

Han received her BA and MS from Peking University in China and her PhD from the University of Illinois.