| First Author | Wang S | Year | 2012 |
| Journal | Nat Med | Volume | 18 |
| Issue | 6 | Pages | 902-10 |
| PubMed ID | 22561688 | Mgi Jnum | J:187465 |
| Mgi Id | MGI:5437167 | Doi | 10.1038/nm.2711 |
| Citation | Wang S, et al. (2012) Activation of AMP-activated protein kinase alpha2 by nicotine instigates formation of abdominal aortic aneurysms in mice in vivo. Nat Med 18(6):902-10 |
| abstractText | Smoking is the only modifiable risk factor that is associated with the development, expansion and rupture of abdominal aortic aneurysm (AAA). However, the causative link between cigarette smoke and AAA is unknown. Here we report a causative link between smoking and AAA in vivo. Acute infusion of angiotensin II (AngII) or nicotine, a major component of cigarette smoke, markedly increased the incidence of AAA in apolipoprotein E (apoE) knockout (Apoe(-/-)) mice and in mice deficient in both apoE and the AMP-activated kinase alpha1 subunit (AMPK-alpha1) (Apoe(-/-); Prkaa1(-/-) mice). In contrast, genetic deletion of AMPK-alpha2 (Apoe(-/-); Prkaa2(-/-) mice) ablated nicotine- or AngII-triggered AAA in vivo. Mechanistically, we found that both nicotine and AngII activated AMPK-alpha2 in cultured vascular smooth muscle cells (VSMCs), resulting in the phosphorylation of activator protein 2alpha (AP-2alpha) and consequent matrix metallopeptidase 2 (MMP2) gene expression. We conclude that smoking (through nicotine) instigates AAA through AMPK-alpha2-mediated AP-2alpha-dependent MMP2 expression in VSMCs. |
