Inflammasomes in the Pathophysiology of Aortic Disease

Abstract

Aortic diseases comprise aneurysms, dissections, and several other pathologies. In general, aging is associated with a slow but progressive dilation of the aorta, along with increased stiffness and pulse pressure. The progression of aortic disease is characterized by subclinical development or acute presentation. Recent evidence suggests that inflammation participates causally in different clinical manifestations of aortic diseases. As of yet, diagnostic imaging and surveillance is mainly based on ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Little medical therapy is available so far to prevent or treat the majority of aortic diseases. Endovascular therapy by the introduction of covered stentgrafts provides the main treatment option, although open surgery and implantation of synthetic grafts remain necessary in many situations. Because of the risks associated with surgery, there is a need for identification of pharmaceutical targets interfering with the pathophysiology of aortic remodeling. The participation of innate immunity and inflammasome activation in different cell types is common in aortic diseases. This review will thus focus on inflammasome activities in vascular cells of different chronic and acute aortic diseases and discuss their role in development and progression. We will also identify research gaps and suggest promising therapeutic targets, which may be used for future medical interventions.

Inflammasome Targeted Therapy as Novel Treatment Option for Aortic Aneurysms and Dissections: A Systematic Review of the Preclinical Evidence

“…Like many cardiovascular diseases, AA and AD have a strong chronic inflammatory phenotype ( 41 ) with a significant involvement of the innate immune system, especially inflammasomes ( 2 ). While in treatment of atherosclerotic cardiovascular diseases anti-inflammatory treatment strategies have been established, so far there is no such treatment option available for treatment of AA and AD.…”

“…Visceral arteries such as the superior mesenteric artery (+) and the right renal artery ( * ) can be affected by the dissection causing organ ischemia. Due to the reduced stability of the aortic wall, most patients with AD require surgical treatment in the long term due to chronic dilatation of the aorta [modified from ( 2 )].…”

“…Although the pathogenesis of AA and AD is still largely unknown, both diseases have a strong inflammatory phenotype ( 2 ). In other cardiovascular diseases, especially atherosclerosis, anti-inflammatory treatment strategies have been successfully established in the last years.…”

“…There is increasing evidence that inflammasomes are involved in the complex inflammatory processes causing emergence and progression of aortic diseases such as AA and AD [reviewed by ( 2 , 13 , 14 )].…”

Type A aortic dissection

“…1,2 Etiologically, AADs can result from congenital causes (structural defect present at birth), genetically determined with onset during childhood or even later, or acquired (inflammatory, degenerative, neoplastic, traumatic). 3,4 From a morphological point of view, the AAD consists of a breach in the thickness of the aorta wall, between the tunica media and the intima, leading to the creation of a 'false lumen' between these two layers, into which blood infiltrates. It rarely remains localized and often progresses by slimming the aortic wall and, in some cases, extending outside the vessel.…”