Inflammasome activity in leucocytes decreases with abdominal aortic aneurysm progression

Abstract

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. The present extended immunohistochemistry study aimed to characterize inflammation in AAA and aortic control samples. In specific, the composition of the infiltrating immune cells and the expression of five inflammasome components in these immune cells were evaluated, in order to characterize their role in AAA development. A total of 104 biopsies from 48 AAA patients and 40 healthy specimens from organ donors were evaluated for their grade of inflammation. Infiltrating leukocytes were characterized by specific markers (CD3, CD20 and CD68), intramural localization and inflammasome protein expression [NLR family pyrin domain containing 3 (NLRP3), absent in melanoma 2 (AIM2), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), Caspase-1 and Caspase-5]. Macrophages, B and T lymphocytes were detected to a similar extent in grade 1, 2 and 3 AAA specimens, whereas in control samples, B and T lymphocytes were rarely observed in grade 1 lesions. Expression frequencies of NLRP3, AIM2 and Caspase-5 were significantly higher in grade 1 lesions of AAA samples compared with grade 1 lesions in control samples. Finally, AIM2, ASC, and Caspase-5 displayed significantly lower expression frequencies in grade 3 compared with grade 2 AAA specimens, and all inflammasome components were less frequently detected in grade 3 than in grade 1 lesions of AAA. This indicates that inflammasome activities decrease with AAA progression in infiltrating leukocytes. No statistically significant association was found for grade 2 and grade 3 lesions and total leukocyte count, C-reactive protein levels, maximal aortic diameter, plasma cholesterol level or biomechanical parameters (derived from finite element analysis) of the respective patients. Overall, the aortic wall of AAA contained lymphocytes and macrophages with different states of activity. The present data suggested that therapeutic inhibition of specific inflammasome components might counteract AAA development and progression.

Abdominal Aortic Aneurysm: Roles of Inflammatory Cells

“…Another study found expression of NLRP3 and AIM2 were notably lower in control samples than AAA. However, with the AAA lesion progression, inflammasome expressions decreased ( 131 ), which suggests the inflammasome-induced signaling plays a more important role in early AAA pathogenesis. Markus et al.…”

Identification of 2 Potential Core Genes for Influence of Gut Probiotics on Formation of Intracranial Aneurysms by Bioinformatics Analysis

“…The KEGG pathways analysis suggested that DEGs were significantly involved in focal adhesion, PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, ECM-receptor interaction, amoebiasis, and chemokine signaling pathway. Previous studies showed that the dysfunction of cell adhesion, immune response, inflammatory response, focal adhesion, PI3K-Akt signaling pathway, chemokine signaling pathway, cytokine-cytokine receptor interaction, and ECM-receptor interaction can cause changes in the vascular structure of aneurysms [25][26][27][28].…”

Importance of NLRP3 Inflammasome in Abdominal Aortic Aneurysms

“…NLRP3 mRNA levels were increased in the aortae of aneurysmal patients as compared to occlusive aortic disease and healthy controls 81) . In another study analyzing aortae from 46 aneurysmal patients and 40 healthy organ donors 82) , more NLRP3-positive staining was noted in the aortae from aneurysmal patients as compared to non-AAA patient controls, with no difference in ASC and caspase 1 staining between two patient groups. However, NLRP3 expression levels were inversely associated with inflammation pathological grade, implying that NLRP3 inflammasome may be an early event in AAA pathogenesis 82) .…”

“…In another study analyzing aortae from 46 aneurysmal patients and 40 healthy organ donors 82) , more NLRP3-positive staining was noted in the aortae from aneurysmal patients as compared to non-AAA patient controls, with no difference in ASC and caspase 1 staining between two patient groups. However, NLRP3 expression levels were inversely associated with inflammation pathological grade, implying that NLRP3 inflammasome may be an early event in AAA pathogenesis 82) . In addition, smooth muscle cells from AAA patients had an increased ability to express NLRP3 and caspase 1 in response to necrotic cell debris 83) .…”