| First Author | Ma H | Year | 2017 |
| Journal | Oncotarget | Volume | 8 |
| Issue | 9 | Pages | 14294-14305 |
| PubMed ID | 28179583 | Mgi Jnum | J:274930 |
| Mgi Id | MGI:6296516 | Doi | 10.18632/oncotarget.15104 |
| Citation | Ma H, et al. (2017) Pravastatin activates activator protein 2 alpha to augment the angiotensin II-induced abdominal aortic aneurysms. Oncotarget 8(9):14294-14305 |
| abstractText | We have previously reported that activation of AMP-activated kinase alpha 2 (AMPKalpha2) by nicotine or angiotensin II (AngII) instigates formation of abdominal aortic aneurysms (AAA) in Apoe-/- mice. Statins, used to treat hyperlipidemia widely, activate AMPK in vascular cells. We sought to examine the effects of pravastatin on AAA formation and uncover the molecular mechanism. The AAA model was induced by AngII and evaluated by incidence, elastin degradation, and maximal abdominal aortic diameter in Apoe-/- mice. The phosphorylated levels of AMPKalpha2 and activator protein 2 alpha (AP-2alpha) were examined in cultured vascular smooth muscle cells (VSMCs) or in mice. We observed that pravastatin (50 mg/kg/day, 8 weeks) remarkably increased the AngII-induced AAA incidence in mice. In VSMCs, pravastatin increased the levels of pAMPK, pAP-2alpha, and MMP2 in both basal and AngII-stressed conditions, which were abolished by tempol and compound C. Pravastatin-upregulated MMP2 was abrogated by AMPKalpha2 or AP-2alpha siRNA. Lentivirus-mediated gene silence of AMPKalpha2 or AP-2alpha abolished pravastatin-worsened AAA formations in AngII-infused Apoe-/- mice. Clinical investigations demonstrated that both AMPKalpha2 and AP-2alpha phosphorylations were increased in AAA patients or human subjects taking pravastatin. In conclusion, pravastatin promotes AAA formation through AMPKalpha2-dependent AP-2alpha activations. |
