The Role of Immune Mechanisms in Abdominal Aortic Aneurysm: Could It be a Promising Therapeutic Strategy?

Abstract

Abdominal aortic aneurysm (AAA) is an enlargement of the aorta greater than 50% in diameter. Although up to 80% of cases result in mortality if the aneurysm ruptures, patients are often diagnosed too late, as most cases are asymptomatic. The current treatment for AAA is still surgery as there are currently no effective drug treatments. Knowledge of the pathophysiological mechanisms is essential for the development of new preventive and therapeutic approaches. However, the molecular mechanisms are complex and remain unclear. Apoptosis of vascular smooth muscle cells, the major cellular component of the aorta, and degeneration of the extracellular matrix, the skeleton of the aortic wall, are hallmarks of AAA pathology. Inflammation, mainly through macrophage cells, has been recognized as a central factor in the development of AAA. Macrophage cells also orchestrate other pathways and immune cells involved in this process. Macrophages do not exist as pure populations at aneurysm sites. M1 macrophages are pro-inflammatory and weaken the aortic wall during AAA development. M2 macrophages, in contrast, are involved in anti-inflammatory reactions and aorta tissue repair. The balancing effect on AAA progression makes M1/M2 macrophages therapeutic targets to control inflammation and destruction of the aortic wall. An early diagnosis is also important to allow for early interventions. This review article, based on the available data, aims to evaluate the role of an immunotherapeutic approach in controlling AAA development by briefly discussing the immunological mechanisms.