Finding new ways to treat aortic aneurysms

MMP-12 inhibition as a therapy for abdominal aortic aneurysm formation and progression

Dr Jason Johnson is working out what causes aortic aneurysms – when the wall of the aorta, the main blood vessel carrying blood from the heart, becomes damaged and weak, and bulges like a balloon. If aneurysms become large they can rupture, causing disability or sudden death. Men over 65 are currently screened in the UK for aneurysms, but there are no effective drug treatments, so we need new ways to treat aortic aneurysms. In an aneurysm, the aorta wall becomes weakened, partly due to cells dying and also due to inflammation. Dr Johnson has found that an enzyme called MMP-12 is present in inflammatory cells called macrophages, and encourages them to invade the vessel wall, suggesting MMP-12 is important in aneurysm development. In this project, he will test a drug that blocks the MMP-12 enzyme in mice to see if it can prevent aneurysms getting worse and even rupturing. He will also study MMP-12 and macrophages in samples from human aneurysms. He will look for new ‘markers’ of aneurysms in the blood, which could reveal a new test to identify people living with an aneurysm. If this research confirms that blocking MMP-12 works, it could form the basis of a new therapy to prevent aneurysms forming and rupturing.