Chronic Inflammatory Signaling in the Development of Aortic Aneurysms

An aneurysm is a weakened section of a major blood vessel wall that expands and remodels into a dilated bulge, vulnerable to rupture and subsequent death. Given that treatment often fails, prevention is of great interest to the research community. What are the contributing factors to the development of an aneurysm? Researchers here look at the contribution of inflammatory signaling, generally agreed upon to be central to the dysregulation of blood vessel tissue that leads to the creation of an aneurysm.

Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years, and it is characterized by the progressive pathological dilatation of the abdominal aortic wall. Most patients who develop AAA are usually asymptomatic; however, when the aneurysm expands and ruptures, its mortality is extremely high. According to reports, even if ruptured AAAs are treated in time, the cases fatality rate is still as high as 50-70%, coupled with the cases without timely surgery, the ruptured AAAs' total mortality can be as high as 90%.

Modern studies have identified aortic extracellular matrix (ECM) degradation, the apoptosis of vascular smooth muscle cells (VSMCs), and vascular chronic inflammatory response as the three basic pathological processes in the pathogenesis of AAA. Of these, vascular chronic inflammatory response is the core process. The cytokines released by inflammatory cells not only exacerbate ECM degradation but also lead to the apoptosis of VSMCs. For example, interleukin (IL)-1β, IL-6, IL-33, and other stimuli prompt macrophages or VSMCs to secrete matrix metalloproteinases (MMPs) that degrade elastin and collagen, leading to the apoptosis of VSMCs and ECM degradation, thereby disrupting the stability of the aortic wall architecture.

It has been demonstrated in animal experiments that the use of an IL-1β receptor inhibitor (anakinra) can effectively inhibit mouse AAA formation induced by porcine pancreatic elastase (PPE) perfusion. Therefore, inflammasome regulation of the secretion of cytokines like IL-1β and IL-18 may significantly influence AAA progression, which has been recognized as a chronic inflammatory disease. This article reviews some mechanism studies to investigate the role of inflammasome in AAA and then summarizes several potential drugs targeting inflammasome for the treatment of AAA, aiming to provide new ideas for the clinical prevention and treatment of AAA beyond surgical methods.


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