Hypoxia-inducible factor 1a induces phenotype switch of human aortic vascular smooth muscle cell through PI3K/AKT/AEG-1 signaling
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Kai Liu1, Changcun Fang1, Yuwen Shen1, Zhengqin Liu1, Min Zhang1, Bingbing Ma1 and Xinyan Pang1
1Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
Xinyan Pang, email: email@example.com
Keywords: HIF-1a, HASMC, PI3K/AKT/AEG-1
Received: December 28, 2016 Accepted: March 09, 2017 Published: March 22, 2017
To date, hypoxia-inducible factor 1a (HIF-1a) and astrocyte elevated gene-1 (AEG-1) have been involved in the proliferation, migration and morphological changes of vascular smooth muscle cells. However, the potential relationship of HIF-1a-AEG-1 pathway in human aortic smooth muscle cell (HASMC) has not been reported. In the present study, in-vitro assays were utilized to explore the potential impact of HIF-1a-AEG-1 signaling on HASMC phenotype. Here, we found that HIF-1a expression was up-regulated in the media of thoracic aortic dissection tissues as compared with normal aortic tissues, and was associated with increased apoptotic SMCs and decreased AEG-1 expression. Mechanically, hypoxia promoted the expression of HIF-1a by PI3K-AKT pathway in HASMCs; HIF-1a further suppressed the expressions of AEG-1, a-SMA and SM22a, and promoted osteopontin (OPN) expression. Functionally, HIF-1a inhibited the proliferation and migration of HASMCs. However, si-HIF-1a or Akt inhibitor abrogated HIF-1a-mediated related expressions and biological effects above. In conclusion, HIF-1a induces HASMC phenotype switch, and closely related to PI3K/AKT and AEG-1 signaling, which may provide new avenues for the prevention and treatment of aortic dissection diseases.
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