title: Increased expression and activation of absent in melanoma 2 inflammasome components in lymphocytic infiltrates of abdominal aortic aneurysms.
abstract: Chronic vascular inflammation is a key hallmark in the pathogenesis of abdominal aortic aneurysm (AAA). Recent investigations have suggested that the inflammasome, a cytosolic multiprotein complex that recognizes pathogen-associated molecular patterns, plays a role in atherosclerosis. However, its role in AAA inflammation has not yet been investigated. This pilot study analyzed inflammasome activation and its intramural localization in 24 biopsy samples from 11 patients with asymptomatic AAA versus 12 aortic samples from apparently healthy controls. Using a histological inflammation scale, we identified grade 2/3 inflammatory changes with lymphoid aggregates/tertiary lymphoid organs in 21 out of 24 AAA samples, whereas only 7 of the 12 control samples exhibited local grade 1 inflammatory changes. Strong expression levels of "apoptosis-associated speck-like protein with a caspase recruitment domain" (ASC), caspase-1, caspase-5 and "absent in melanoma 2" (AIM2) were detected by immunohistochemistry in both sporadic infiltrating lymphoid cells and lymphoid aggregates located in the outer media and adventitia of AAA samples. In contrast, inflammasome-positive cells were restricted to cholesterol plaque-associated areas and to single infiltrating cells in control aortas. Analysis of gene expression using real-time polymerase chain reaction (PCR) revealed significantly increased median mRNA levels of the inflammasome core components PYCARD (ASC), CASP1 (Caspase-1) and IL1B (IL-1β) in AAA tissue compared with normal aorta. Moreover, significantly increased median amounts of AIM2 protein and mature caspase-5 (p20) were found in samples associated with high rupture risk compared with paired low rupture risk samples of the same AAA patient. We conclude from our data that AAA-associated lymphoid cells are capable of inflammasome signaling, suggesting that inflammasome activation is involved in the chronic inflammatory process driving AAA progression.
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Dihlmann
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Erhart
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Arianeb
authors.initials: A
authors.lastname: Mehrabi
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Arash
authors.initials: A
authors.lastname: Nickkholgh
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Lasitschka
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Dittmar
authors.initials: D
authors.lastname: Böckler
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Maani
authors.initials: M
authors.lastname: Hakimi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000276:immunology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology* / Q000473:pathology; D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D020169:Caspases / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: C410167:AIM2 protein, human; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D058847:Inflammasomes; C402202:PYCARD protein, human; C099217:CASP5 protein, human; D020169:Caspases; D020170:Caspase 1