Innovative Model Paves the Way for Better Understanding of Hypertension and Aortic Aneurysms

Researchers at Mass General Brigham have made significant progress in understanding and potentially treating hypertension and aortic aneurysms by developing a novel laboratory model to study these vascular conditions. Oxidative stress, caused by reactive oxygen species damaging cellular components, has long been associated with cardiovascular diseases such as high blood pressure and aortic aneurysms—balloon-like expansions of the aorta that can be fatal if ruptured. However, whether oxidative stress is a cause or merely a consequence has remained uncertain.

The team created a transgenic mouse model that allows for the dynamic control of oxidative stress within blood vessels using a new approach called chemogenetics. This innovative method enables scientists to manipulate specific cellular processes in real-time, shedding light on the role of oxidative stress in vascular diseases.

Their investigations revealed that oxidative stress leads to modifications in proteins within the blood vessel walls, prompting vascular cells to change and increase their susceptibility to aneurysm formation and hypertension. A key protein identified in this pathway is DUSP-3. When an inhibitor targeting DUSP-3 was administered to mice experiencing oxidative stress, the development of aortic aneurysms and high blood pressure was effectively halted.

These findings suggest that DUSP-3 represents a promising new target for treating these conditions. Senior author Dr. Thomas Michel emphasized that this discovery may open avenues for novel therapies, noting, "Our studies have identified a potentially important and entirely new drug target for the prevention and treatment of hypertension and aortic aneurysms."

The research also explored whether oxidative stress directly causes vascular diseases. Their results demonstrated that mitigating oxidative stress via DUSP-3 inhibition successfully prevented disease progression, pointing to oxidative stress as a causal factor rather than just a byproduct.

This groundbreaking work not only enhances understanding of the mechanisms behind vascular diseases but also offers hope for developing targeted treatments that could significantly reduce mortality and morbidity associated with hypertension and aortic aneurysms. The full study is published in The Journal of Clinical Investigation.