| First Author | Tsai SH | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 28612 | PubMed ID | 27363580 |
| Mgi Jnum | J:254434 | Mgi Id | MGI:6101562 |
| Doi | 10.1038/srep28612 | Citation | Tsai SH, et al. (2016) Inhibition of hypoxia inducible factor-1alpha attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases. Sci Rep 6:28612 |
| abstractText | Hypoxia inducible factor-1alpha (HIF-1alpha) pathway is associated with many vascular diseases, including atherosclerosis, arterial aneurysms, pulmonary hypertension and chronic venous diseases. Significant HIF-1alpha expression could be found at the rupture edge at human abdominal aortic aneurysm (AAA) tissues. While our initial in vitro experiments had shown that deferoxamine (DFO) could attenuate angiotensin II (AngII) induced endothelial activations; we unexpectedly found that DFO augmented the severity of AngII-induced AAA, at least partly through increased accumulation of HIF-1alpha. The findings promoted us to test whether aneurysmal prone factors could up-regulate the expression of MMP-2 and MMP-9 through aberrantly increased HIF-1alpha and promote AAA development. AngII induced AAA in hyperlipidemic mice model was used. DFO, as a prolyl hydroxylase inhibitor, stabilized HIF-1alpha and augmented MMPs activities. Aneurysmal-prone factors induced HIF-1alpha can cause overexpression of MMP-2 and MMP-9 and promote aneurysmal progression. Pharmacological HIF-1alpha inhibitors, digoxin and 2-ME could ameliorate AngII induced AAA in vivo. HIF-1alpha is pivotal for the development of AAA. Our study provides a rationale for using HIF-1alpha inhibitors as an adjunctive medical therapy in addition to current cardiovascular risk-reducing regimens. |
