New Hope for Hypertension and Aortic Aneurysms: Targeting Oxidative Stress with DUSP-3 Inhibition
Could a newly discovered pathway hold the key to preventing and treating two life-threatening conditions – high blood pressure (hypertension) and aortic aneurysms? Groundbreaking research from Mass General Brigham, published May 1, 2025, in the Journal of Clinical Investigation, suggests precisely that. This isn’t just incremental progress; it’s the identification of a potentially novel drug target, offering a beacon of hope for millions affected by these conditions.
the Silent threats: Hypertension and Aortic Aneurysms
Hypertension, affecting nearly half of all adults in the United States, remains a major public health crisis. According to the CDC, approximately 116.4 million Americans have high blood pressure as of 2023 https://www.cdc.gov/bloodpressure/index.htm. Often dubbed the “silent killer,” it frequently goes undetected until serious complications arise.
One such complication is the aortic aneurysm – a perilous ballooning of the aorta, the body’s largest artery. These aneurysms are often asymptomatic until they rupture, a catastrophic event with a mortality rate exceeding 70%. Approximately 15,000 Americans tragically lose their lives to aortic aneurysms annually, highlighting the urgent need for improved understanding and treatment options. The underlying causes of these aneurysms have remained elusive, hindering the development of effective preventative measures.
Unraveling the Connection: Oxidative Stress and Vascular Disease
For years, scientists have suspected a link between oxidative stress – an imbalance between the production of free radicals and the body’s ability to neutralize them – and the development of both hypertension and aortic aneurysms. Reactive oxygen species (ROS), the molecules responsible for oxidative stress, can inflict significant damage on cells over time. However, proving a causal relationship has been a major challenge.
Researchers led by Dr. Thomas Michel at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, have overcome this hurdle. Their innovative approach involved creating a unique transgenic mouse model utilizing a technique called “chemogenetics.” This allowed them to dynamically control oxidative stress levels within blood vessels, providing an unprecedented level of precision in their investigations.
DUSP-3: The Newly Identified Key Player
The team, spearheaded by postdoctoral fellow Dr. Apabrita ayan Das, discovered that oxidative stress triggers changes in proteins within the blood vessel walls, making them more susceptible to aneurysm formation and contributing to hypertension. Crucially, they pinpointed a specific protein, DUSP-3 (Dual Specificity Phosphatase 3), as a central player in this damaging process.
Remarkably, when mice experiencing oxidative stress were treated with a DUSP-3 inhibitor, the development of aortic aneurysms was blocked, and hypertension was substantially reduced. This finding is notably exciting because DUSP-3 had never before been linked to either condition.
“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,” explains Dr. Michel,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.”
Beyond Hypertension and Aneurysms: The Broader Implications
The potential impact of this finding extends far beyond hypertension and aortic aneurysms. The researchers are now investigating whether inhibiting DUSP-3 can also offer therapeutic benefits in other vascular diseases linked to oxidative stress, including:
Alzheimer’s Disease: Oxidative stress is a known contributor to neurodegeneration.
Atherosclerosis: The buildup of plaque in arteries is exacerbated by oxidative damage.
Aging: Oxidative stress accumulates with age, contributing to various age-related diseases.
This suggests that targeting DUSP-3 could represent a broad-spectrum approach to combating a range of conditions driven by oxidative stress.
What Does This Mean for Patients?
While this research is still in its early stages, it offers a significant leap forward in our understanding of these complex diseases. it’s important to remember that this study was conducted in mice, and further research is needed to confirm these findings in humans.However, the identification of DUSP-3 as a potential drug target opens the door to the development of new and more effective therapies.
What can you do now to protect your vascular health?
Monitor your blood pressure regularly. Early detection is key to managing hypertension.
* Adopt a heart-healthy lifestyle: This includes a
