title: Silencing of hypoxia inducible factor-1α gene attenuated angiotensin Ⅱ-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice.
abstract: We aimed to determine the effect of HIF-1α, the main regulatory subunit of the hypoxia inducible factor 1 (HIF-1), on the development of the abdominal aortic aneurysm (AAA).
  
  
  
  AAA was induced in ApoE(-/-) mice by angiotensinⅡ (AngⅡ) infusion. In vivo silencing of HIF-1α was achieved by transfection of lentivirus expressing HIF-1α shRNA.
  
  
  
  Time course analysis of the AngⅡ infusion model revealed that HIF-1α was persistently upregulated during a 28-day period of AAA development. Silencing of the HIF-1α 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-1α 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 AngⅡ infusion model, at day 28. The activity of MMP-2 and MMP-9 was also decreased by knockdown of HIF-1α. The early increased expression of pro-inflammatory factors, angiogenic factors, and MMPs during AAA induction was alleviated by HIF-1α silencing.
  
  
  
  Activation of HIF-1 signaling pathway participates in the Ang Ⅱ-induced AAA formation in mice.
authors: Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors: Le
authors: L
authors: Yang
authors: Department of Ophthalmology, QiLu Hospital to Shandong University, Jinan, China.
authors: Lin
authors: L
authors: Shen
authors: Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors: Gang
authors: G
authors: Li
authors: Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors: Hai
authors: H
authors: Yuan
authors: Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. Electronic address: sdujinxing@163.com.
authors: Xing
authors: X
authors: Jin
authors: Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. Electronic address: wuxuejun0704@163.com.
authors: Xuejun
authors: X
authors: Wu
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D004195:Disease Models, Animal; D020868:Gene Silencing; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007249:Inflammation; D016086:Lentivirus; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D008833:Microcirculation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D000804:Angiotensin II
keywords: Abdominal aortic aneurysm; HIF-1α; Inflammation; MMP; Neovascularity