Le Yang1, Lin Shen2, Gang Li1, Hai Yuan1, Xing Jin3, Xuejun Wu4. 1. Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. 2. Department of Ophthalmology, QiLu Hospital to Shandong University, Jinan, China. 3. Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. Electronic address: sdujinxing@163.com. 4. Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. Electronic address: wuxuejun0704@163.com.
Abstract
BACKGROUND AND AIMS: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Activation of HIF-1 signaling pathway participates in the Ang Ⅱ-induced AAA formation in mice.
BACKGROUND AND AIMS: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Activation of HIF-1 signaling pathway participates in the Ang Ⅱ-induced AAA formation in mice.
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