Autoimmunity in the Abdominal Aortic Aneurysm and its Association with Smoking

Smoking increases the risk of abdominal aortic aneurysm (AAA) in both humans and mice, although the underlying mechanisms are not completely understood. An adventitial aortic antigen, AAAP-40, has been partially sequenced. It has motifs with similarities to all three fibrinogen chains and appears to be connected in evolution to a large family of proteins called fibrinogen-related proteins. Fibrinogen may undergo non-enzymatic nitration, which may result from exposure to nitric oxide in cigarette smoke. Nitration of proteins renders them more immunogenic. It has recently been reported that anti-fibrinogen antibody promotes AAA development in mice. Also, anti-fibrinogen antibodies are present in patients with AAA. These matters are reviewed in the overall context of autoimmunity in AAA. The evidence suggests that smoking amplifies an auto-immune reaction that is critical to the pathogenesis of AAA.