Chronic inflammation, immune response, and infection in abdominal aortic aneurysms.
Abdominal aortic aneurysms (AAA) are associated with atherosclerosis, transmural degenerative processes, neovascularization, decrease in content of vascular smooth muscle cells, and a chronic infiltration, mainly located in the outer aortic wall. The chronic infiltration consists mainly of macrophages, lymphocytes, and plasma cells. The dominant cells are Th2 restricted CD3+ lymphocytes expressing interleukine 4, 5, 8, and 10, and tumor necrosis factor-alpha for regulation of the local immune response. They also produce interferon-gamma and CD40 ligand to stimulate surrounding cells to produce matrix metalloproteases and cysteine proteases for aortic matrix remodeling. The lymphocyte activation may be mediated by microorganisms as well as autoantigens generated from vascular structural proteins, perhaps through molecular mimicry. As in autoimmune diseases, the risk of AAA is increased by certain genotypes concerning human leucocyte antigen class II. These types are also associated with increased aneurysmal inflammation indicating a genetic susceptibility to aortic inflammation. Chlamydia pneumoniae is often detected in AAA but the validity of the methods can be questioned, and two small antibiotic trials have been disappointing. However, serum antibodies against C. pneumoniae have been associated with AAA growth and cross-react with AAA wall proteins. Thus, immune responses mediated by microorganisms and autoantigens may play a pivotal role in AAA pathogenesis.
Lindholt
J S
JS
Vascular Research Unit, Department of Vascular Surgery, Viborg Hospital, Viborg, Denmark. jes.s.lindholt@sygehusviborg.dk
Shi
G-P
GP
D017544:Aortic Aneurysm, Abdominal / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000503:physiopathology