Abstract
BackgroundHypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells (VSMC) functions. Macrophage migration inhibitory factor (MIF) is a well known proinflammatory factor, and recent evidence suggests an important role of MIF in the progression of atherosclerosis and restenosis. However, the potential link between hypoxia and MIF in VSMC has not been investigated. The current study was designed to test whether hypoxia could regulate MIF expression in human VSMC. The effect of modulating MIF expression on hypoxia-induced VSMC proliferation and migration was also investigated at the same time.ResultsExpression of MIF mRNA and protein was up-regulated as early as 2 hours in cultured human VSMCs after exposed to moderate hypoxia condition (3% O2). The up-regulation of MIF expression appears to be dependent on hypoxia-inducible transcription factor-1α(HIF-1α) since knockdown of HIF-1α inhibits the hypoxia induction of MIF gene and protein expression. The hypoxia induced expression of MIF was attenuated by antioxidant treatment as well as by inhibition of extracellular signal-regulated kinase (ERK). Under moderate hypoxia conditions (3% O2), both cell proliferation and cell migration were increased in VSMC cells. Blocking the MIF by specific small interference RNA to MIF (MIF-shRNA) resulted in the suppression of proliferation and migration of VSMCs.ConclusionOur results demonstrated that in VSMCs, hypoxia increased MIF gene expression and protein production. The hypoxia-induced HIF-1α activation, reactive oxygen species (ROS) generation and ERK activation might be involved in this response. Both MIF and HIF-1α mediated the hypoxia response of vascular smooth muscle cells, including cell migration and proliferation.
Highlights
Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells (VSMC) functions
The hypoxia-induced migration inhibitory factor (MIF) expression in cultured vascular smooth muscle cells is dependent on HIF-1a pathway we investigated whether HIF-1a was involved in hypoxia-induced MIF upregulation in human umbilical artery smooth muscle cells (HUASMCs)
Inhibition of ERK by its specific inhibitor PD98059 significantly decreased hypoxia-induced MIF expression at both gene and protein levels (Figure 5). These findings suggest that hypoxia-induced MIF expression in HUASMCs is mediated by reactive oxygen species and extracellular signal-regulated kinase signaling
Summary
Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells (VSMC) functions. The potential link between hypoxia and MIF in VSMC has not been investigated. The current study was designed to test whether hypoxia could regulate MIF expression in human VSMC. The effect of modulating MIF expression on hypoxia-induced VSMC proliferation and migration was investigated at the same time. The cellular effects of hypoxia are primarily mediated by the hypoxia-inducible transcription factor-1 (HIF-1). It is a heterodimeric transcription factor composed of a and b subunits. The role of hypoxia and HIF-1 in atherosclerosis remains largely unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
