Dale Matthew A, Ruhlman Melissa K, Baxter B Timothy
From the Department of Pathology and Microbiology (M.A.D.) and Department of Surgery, University of Nebraska Medical Center, Omaha (M.A.D., M.K.R., B.T.B.).
Arterioscler Thromb Vasc Biol. 2015 Aug;35(8):1746-55. doi: 10.1161/ATVBAHA.115.305269. Epub 2015 Jun 4.
Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. 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. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory 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 proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention.
腹主动脉瘤(AAA)的特征是慢性炎症细胞浸润。AAA通常是一种无症状疾病,在美国每年导致约15000人死亡。先前的研究已经在人类和小鼠主动脉组织中检测了各种炎症细胞类型的存在。研究表明,在人类和实验性AAA中,受损的主动脉壁都会出现显著的炎症细胞浸润,如CD4(+) T细胞和巨噬细胞。这些细胞能够根据微环境线索进行表型调节,可能影响疾病进展。促炎性CD4(+) T细胞和经典活化的巨噬细胞在主动脉浸润细胞中占主导地位。向促炎表型的转变会改变疾病进展,并在引起慢性炎症中起作用。局部细胞因子的产生以及炎症介质(如细胞外基质降解产物)的存在,影响了炎症浸润表型的不均衡平衡。了解并开发针对促炎表型的新策略,可为目前尚无药物干预的疾病提供有用的治疗靶点。