Stroke and heart attack are two of our most common and serious diseases, caused by damage to the walls of blood vessels, with high blood pressure being a key driver. We have shown that the proteins YAP and TAZ help blood vessel muscle cells adapt to pressure and that this is essential for short-term survival. The Hippo system slows down YAP and TAZ, but the role of Hippo in stroke, vascular rupture and heart attack has not been studied. Our research approach aims to change that. We want to show that the Hippo system plays a crucial role in the natural protection of blood vessels against mechanical damage, a protection that could also become a new route to treatment. We have four goals which include (1) identifying key proteins of the Hippo system in arteries, (2) developing a novel mouse model, (3) testing whether blocking Hippo can protect against stroke, aneurysm and plaque rupture, and (4) developing a genetic risk index to show the link between the Hippo system and stroke/heart attack in humans.