Inflammatory Cell Phenotypes in AAAs

Abstract

Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention.

Impending aortic aneurysm rupture – a case report and review of the warning signs

“…The pathogenesis of AAA is a multifactorial process, with underlying genetic, inflammatory, and autoimmune components (7, 8). After an aneurysm has formed, many factors associated with greater risk of rupture have been identified including maximum diameter of the aneurysm, rate of increase in aneurysm size, hypertension, age, smoking history, COPD, bronchiectasis, and family history of aneurysms (9–11).…”

Aortic Aneurysms

“…27,29 A spectrum of potential mechanisms of AAA have been studied using these mouse models in their original or modified forms. 11,12,30–34 …”

“…Inflammation is a common characteristic of AAA lesions, 11,16,35,36 which is manifested by inflammatory cell accumulation and a wide range of inflammatory molecular and signaling changes.…”

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

“…In addition, we have recently demonstrated elevated levels of inflammasome components in lymphocytic infiltrates of AAA (8). Assembly of these inflammasomes is in turn required for Caspase-1-dependent processing on histopathological features of AAA from human tissue and animal studies, potential targets for prediction of the individual rupture risk and for efficient pharmaceutical interventions to attenuate expansion remain to be identified (1,2).…”