| First Author | Yang L | Year | 2016 |
| Journal | Atherosclerosis | Volume | 252 |
| Pages | 40-49 | PubMed ID | 27497884 |
| Mgi Jnum | J:315456 | Mgi Id | MGI:6830472 |
| Doi | 10.1016/j.atherosclerosis.2016.07.010 | Citation | Yang L, et al. (2016) Silencing of hypoxia inducible factor-1alpha gene attenuated angiotensin -induced abdominal aortic aneurysm in apolipoprotein E-deficient mice. Atherosclerosis 252:40-49 |
| abstractText | BACKGROUND AND AIMS: We aimed to determine the effect of HIF-1alpha, the main regulatory subunit of the hypoxia inducible factor 1 (HIF-1), on the development of the abdominal aortic aneurysm (AAA). METHODS: AAA was induced in ApoE(-/-) mice by angiotensin (Ang) infusion. In vivo silencing of HIF-1alpha was achieved by transfection of lentivirus expressing HIF-1alpha shRNA. RESULTS: Time course analysis of the Ang infusion model revealed that HIF-1alpha was persistently upregulated during a 28-day period of AAA development. Silencing of the HIF-1alpha gene reduced the aneurysm size (2.84 +/- 1.96 mm vs. 1.41 +/- 0.85 mm respectively at day 28, p = 0.0002). Silencing of HIF-1alpha also alleviated infiltration of macrophages (38.8 +/- 14.7 vs. 11.4 +/- 4.4 macrophages/0.1 mm(2), p = 0.0006) and neovascularity (5.56 +/- 2.14 vs. 1.27 +/- 1.05 microvessels/0.1 mm(2), p = 0.0008) in the Ang infusion model, at day 28. The activity of MMP-2 and MMP-9 was also decreased by knockdown of HIF-1alpha. The early increased expression of pro-inflammatory factors, angiogenic factors, and MMPs during AAA induction was alleviated by HIF-1alpha silencing. CONCLUSIONS: Activation of HIF-1 signaling pathway participates in the Ang -induced AAA formation in mice. |
