OSE-IgM in AAA

Cardiovascular diseases are characterized by inflammatory processes which result in the modification of molecules, thereby generating so-called oxidation specific epitopes (OSEs) that are recognized by our immune system. Natural antibodies (IgM) against OSEs have been recognized for their protective effect in atherosclerotic disease. In contrast, little is known about the role of OSE-specific antibodies in abdominal aortic aneurysms (AAAs) which share many features of atherosclerosis. AAA is a progressive dilatation of the abdominal aorta due to the weakening of the vessel wall. It constitutes a serious condition with the risk of aorta rupture and sudden death. Yet, it lacks approved drug treatments and can only be surgically repaired. Since we found OSEs and OSE IgM in (human and mouse) aneurysm tissue, we developed the hypothesis that AAA formation involves oxidative processes which result in OSE accumulation at the aneurysm site and trigger a rise in OSE-specific antibodies. In the current project we aim to investigate the contribution of OSE IgM to AAA development and their therapeutic potential. To this end, we will primarily conduct experiments in two mouse models of AAA (which cover distinct aspects of human disease). We will elucidate the impact of reduced or elevated levels of natural antibodies, in particular OSE IgM, in these AAA models. Furthermore, OSE IgM will be investigated in clinical samples, comparing healthy individuals, patients with AAA or non-aneurysmal atherosclerotic disease. Elucidating the hitherto unexplored role of OSE IgM in AAA may not only provide a tool to predict aneurysm growth and thus identify patients who would benefit from early surgical intervention, but may also offer novel insights into the mechanism of AAA development and help establish new non-surgical therapeutic interventions.