OBJECTIVE: Hypoxia-inducible factor (HIF)-1alpha is the regulatory subunit of a transcriptional complex, which controls the recruitment of multipotent progenitor cells and tissue repair in ischemic tissue by inducing stromal cell-derived factor (SDF)-1alpha expression. Because HIF-1alpha can be activated under normoxic conditions in smooth muscle cells (SMCs) by platelet products, we investigated the role of HIF-1alpha in SDF-1alpha-mediated neointima formation after vascular injury. METHODS AND RESULTS: Wire-induced injury of the left carotid artery was performed in apolipoprotein E-deficient mice. HIF-1alpha expression was increased in the media as early as 1 day after injury, predominantly in SMCs. Nuclear translocation of HIF-1alpha and colocalization with SDF-1alpha was detected in neointimal cells after 2 weeks. HIF-1alpha mRNA expression was induced at 6 hours after injury as determined by real-time RT-PCR. Inhibition of HIF-1alpha expression by local application of HIF-1alpha-siRNA reduced the neointimal area by 49% and significantly decreased the neointimal SMCs content compared with control-siRNA. HIF-1alpha and SDF-1alpha expression were clearly diminished in neointimal cells of HIF-1alpha-siRNA treated arteries. CONCLUSIONS: HIF-1alpha expression is directly involved in neointimal formation after vascular injury and mediates the upregulation of SDF-1alpha, which may affect the stem cell-based repair of injured arteries.
OBJECTIVE:Hypoxia-inducible factor (HIF)-1alpha is the regulatory subunit of a transcriptional complex, which controls the recruitment of multipotent progenitor cells and tissue repair in ischemic tissue by inducing stromal cell-derived factor (SDF)-1alpha expression. Because HIF-1alpha can be activated under normoxic conditions in smooth muscle cells (SMCs) by platelet products, we investigated the role of HIF-1alpha in SDF-1alpha-mediated neointima formation after vascular injury. METHODS AND RESULTS: Wire-induced injury of the left carotid artery was performed in apolipoprotein E-deficient mice. HIF-1alpha expression was increased in the media as early as 1 day after injury, predominantly in SMCs. Nuclear translocation of HIF-1alpha and colocalization with SDF-1alpha was detected in neointimal cells after 2 weeks. HIF-1alpha mRNA expression was induced at 6 hours after injury as determined by real-time RT-PCR. Inhibition of HIF-1alpha expression by local application of HIF-1alpha-siRNA reduced the neointimal area by 49% and significantly decreased the neointimal SMCs content compared with control-siRNA. HIF-1alpha and SDF-1alpha expression were clearly diminished in neointimal cells of HIF-1alpha-siRNA treated arteries. CONCLUSIONS:HIF-1alpha expression is directly involved in neointimal formation after vascular injury and mediates the upregulation of SDF-1alpha, which may affect the stem cell-based repair of injured arteries.
Authors: Ilze Bot; Isabelle T M N Daissormont; Alma Zernecke; Gijs H M van Puijvelde; Birgit Kramp; Saskia C A de Jager; Judith C Sluimer; Marco Manca; Veronica Hérias; Marijke M Westra; Martine Bot; Peter J van Santbrink; Theo J C van Berkel; Lishan Su; Mona Skjelland; Lars Gullestad; Johan Kuiper; Bente Halvorsen; Paul Aukrust; Rory R Koenen; Christian Weber; Erik A L Biessen Journal: J Mol Cell Cardiol Date: 2014-05-08 Impact factor: 5.000
Authors: Anush V Karapetyan; Yuri M Klyachkin; Samy Selim; Manjula Sunkara; Khaled M Ziada; Donald A Cohen; Ewa K Zuba-Surma; Janina Ratajczak; Susan S Smyth; Mariusz Z Ratajczak; Andrew J Morris; Ahmed Abdel-Latif Journal: Stem Cells Dev Date: 2013-02-19 Impact factor: 3.272