Abstract
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.
Highlights
As is known to all, vascular smooth muscle cells (VSMCs) act as a key member in the media of human aorta, which have two kinds of cell phenotypes, including contractile and synthetic status
Hypoxia promoted the expression of HIF1α by PI3K-AKT pathway in human aortic smooth muscle cell (HASMC); hypoxia-inducible factor 1α (HIF-1α) further suppressed the expressions of astrocyte elevated gene-1 (AEG-1), α-SMA and smooth muscle 22α (SM22α), and promoted osteopontin (OPN) expression
We used qRT-PCR and western blot to analyze the expression of HIF-1α in aortic SMCs of thoracic aortic dissection (TAD) specimens
Summary
As is known to all, vascular smooth muscle cells (VSMCs) act as a key member in the media of human aorta, which have two kinds of cell phenotypes, including contractile and synthetic status. Contractile VSMCs have a poor capacity of proliferation and migration, and showed a spindle-like model. Contractile VSMCs were very hard to generate extracellular matrix [1,2,3,4]. Synthetic VSMCs have a stronger ability of proliferation, migration and synthesis of extracellular matrix, including collagen, elastin, and proteoglycans [4, 5]. Like atherosclerosis, hypertension, and aortic dissection, contractile VSMCs are able to change into synthetic VSMCs, which could trigger the migration, proliferation and synthesis of extracellular matrix of VSMCs [5, 6, 8, 9]. Some extracellular factors and downstream signaling are implicated into this switch of VSMCs [4, 5, 8, 10,11,12]
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