Nat med：尼古丁促腹主动脉瘤形成

Abdominal aortic aneurysm is an enlargement of the abdominal aorta that represents a difficult clinical problem because the initial symptom is often rupture of the aneurysm1, an event with a mortality exceeding 70% (ref. 2), despite advances in surgical treatment3. These aneurysms start as small dilatations of the abdominal aorta that gradually expand over the course of years with the risk of rupture increasing drastically once the aneurysm reaches a diameter of 5 cm or more. The only accepted treatment for these large aneurysms is surgical open or endovascular graft placement. Early detection of smaller abdominal aneurysms is important because it enables clinicians to observe aneurysm expansion and intervene before rupture. However, prophylactic surgery for aneurysms smaller than 5 cm has not proven useful, so the current practice is watchful waiting until intervention is possible, and most aneurysms slowly expand over years.

Epidemiologic data have clearly linked tobacco smoking to aneurysm formation and a faster rate of expansion1, 4. Pathological examination of human abdominal aortic aneurysm tissue has shown that it is characterized by intense oxidative stress, inflammation and matrix degradation5, 6, but the mechanistic relationship linking aneurysm formation to smoking has remained elusive.

In this issue of Nature Medicine, Wang et al.7 break this impasse and provide new insights into the link between tobacco smoking and abdominal aortic aneurysms (Fig. 1). Using mouse models, they found that nicotine, the main dependence-forming ingredient of tobacco, increases aneurysm formation by stimulating the α2 isoform of AMP-activated protein kinase (AMPKα2) in vascular smooth muscle cells (VSMCs). Activation of AMPKα2, in turn, resulted in phosphorylation of activator protein 2α, a transcription factor that drives the expression of and smooth muscle cell release of matrix metalloproteinase 2, a matrix-degrading protein that functions to weaken the artery wall, thus facilitating aneurysm formation8.