Cytokines in Abdominal Aortic Aneurysm: Master Regulators With Clinical Application

Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder with a mostly asymptomatic course where the abdominal aorta is weakened and bulged. Cytokines play especially important roles (both positive and negative) among the molecular actors of AAA development. All the inflammatory cascades, extracellular matrix degradation and vascular smooth muscle cell apoptosis are driven by cytokines. Previous studies emphasize an altered expression and a changed epigenetic regulation of key cytokines in AAA tissue samples. Such cytokines as IL-6, IL-10. IL-12, IL-17, IL-33, IL-1 beta, TGF-beta, TNF-alpha, IFN-gamma, and CXCL10 seem to be crucial in AAA pathogenesis. Some data obtained in animal studies show a protective function of IL-10, IL-33, and canonical TGF-beta signaling, as well as a dual role of IL-4, IFN-gamma and CXCL10, while TNF-alpha, IL-1 beta. IL-6, IL-12/IL-23, IL-17, CCR2, CXCR2, CXCR4 and the TGF-11 noncanonical pathway are believed to aggravate the disease. Altogether data highlight significance of cytokines as informative markers and predictors of AM. Pathologic serum/plasma concentrations of IL-113. IL-2, IL-6, TNF-alpha. IL-10. IL-8, IL-17, IFN-gamma, and PDGF have been already found in MA patients. Some of the changes correlate with the size of aneurysms. Moreover, the risk of MA is associated with polymorphic variants of genes encoding cytokines and their receptors: CCR2 (rs1799864). CCR5 (Delta-32), IL6 (rs1800796 and rs1800795), IL6R (rs12133641). IL10 (rs1800896), TGFB1 (rs1800469). TGFBR1 (rs1626340). TGFBR2 (rs1036095, rs4522809, rs1078985). and TNFA (rs1800629), Finally, 5 single-nucleotide polymorphisms in gene coding latent TGF-beta-binding protein (LTBP4) and an allelic variant of TGFB3 are related to a significantly slower AM annual growth rate.

Automated summary

Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder where the abdominal aorta becomes weakened and bulged. Cytokines, including IL-6, IL-10, IL-12, IL-17, IL-33, IL-1 beta, TGF-beta, TNF-alpha, IFN-gamma, and CXCL10, play important roles in the development of AAA. Changes in the expression and regulation of these cytokines in AAA tissue samples have been observed. These cytokines can serve as informative markers and predictors of AAA, and their abnormal concentrations have been found in patients with AAA. Polymorphic variants of genes encoding cytokines and their receptors are also associated with the risk of AAA.