Immune and inflammatory mechanisms of abdominal aortic aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. Immune-mediated infiltration and a destruction of the aortic wall during AAA development plays significant role in the pathogenesis of this disease. While various immune cells had been found in AAA, the mechanisms of their activation and function are still far from being understood. A better understanding of mechanisms regulating the development of aberrant immune cell activation in AAA is essential for the development of novel preventive and therapeutic approaches. In this review we summarize current knowledge about the role of immune cells in AAA and discuss how pathogenic immune cell activation is regulated in this disease.

Keywords: abdominal aortic aneurysm; cytokines; immune cells; inflammation; microbiota; tissue microenvironment; vascular immunology.

Figure 1

Immune networks in aortic abdominal aneurysm. Various immune cells are found in the aorta with AAA. The composition and activation status of immune cells infiltrating the aortic wall during AAA development is dynamic and changes through the course of disease development. Activated immune cells contribute to the inflammatory environment in the aortic wall and VSMC apoptosis resulting in the destruction of the aorta and progressive growth of AAA eventually leading to rupture. NK, Natural Killer; MF, macrophages; Tregs, T regulatory cells; NF, neutrophils; γδ T cells, Th17, T helper 17 cells; Th1, T helper 1 cells; Th2, T helper 2 cells; DC, dendritic cells; VSMC, vascular smooth muscle cells; IgM, immunoglobulin M; IgG, immunoglobulin G; MMPs, matrix metalloproteinases; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, Interleukin; ECM, Extracellular Matrix; AT1aR, Angiotensin II Receptor Type 1; TLR, Toll-like Receptor; PVAT, perivascular adipose tissue; Ang II, Angiotensin II.

Figure 2

Potential mechanisms regulating immune cells activation in AAA. Multiple factors may systemically and locally regulate immune cells activation in AAA. Angiotensin (Ang) II receptors are expressed on various immune cells and can directly regulate their activation and function. Alteration of intestinal barrier will impact microbiota composition and function leading to changes in circulating metabolites and microbial products that in turn may regulate immune cell activation in AAA. Ang II as well as microbiota-derived products may stimulate immune cell mobilization from bone marrow and spleen. Perivascular adipose tissue (PVAT) may contribute to the inflammation in the aortic wall via the production of adipokines, cytokines and chemokines regulating immune cells accumulation in PVAT.