New model to study hypertension and aortic aneurysms developed

Investigators at Mass General Brigham have discovered a new pathway that may lead to a treatment for high blood pressure and aortic aneurysms. By creating a new laboratory model for studying these conditions, the team treated hypertension and aortic aneurysms by targeting a protein that they discovered to be involved in the vascular cells' response to oxidative stress. The findings are published on May 1, 2025 in The Journal of Clinical Investigation.

"Each year, approximately 15,000 Americans die from aortic aneurysms, yet the causes of aortic aneurysms are incompletely understood. And hypertension -- high blood pressure -- affects half of all adults in this country, and there is a large unmet need for the development of new antihypertensive drugs," said senior author Thomas Michel, MD, PhD, who is a senior physician in Cardiovascular Medicine at Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system. Michel is also a professor at Harvard Medical School. "Our studies have identified a potentially important and entirely new drug target for the prevention and treatment of hypertension and aortic aneurysms."

Although oxidative stress has long been associated with hypertension and aortic aneurysms, it was unclear whether it actually causes these complex medical conditions. To investigate, Michel and his colleagues created a transgenic mouse model in which oxidative stress can be dynamically modulated within blood vessels using a new scientific strategy termed "chemogenetics."

The studies, led by Apabrita Ayan Das, PhD, a postdoctoral research fellow in the Michel laboratory, found that oxidative stress affected proteins in the blood vessel walls, causing vascular cells to change and become more prone to aneurysms and hypertension. The research team found that one of the key players in this process is a protein called DUSP-3. When the scientists gave mice with oxidative stress an inhibitor of DUSP-3, the treatment blocked the development of aortic aneurysms and reduced hypertension.

"DUSP-3 had never previously been implicated in hypertension or aneurysm formation. It could be an important drug target to treat or prevent these conditions," said Michel. "We are also expanding our studies of DUSP-3 inhibition to study other vascular disease states associated with oxidative stress, including Alzheimer's disease, atherosclerosis, and aging."