Expression of HIF-1 in Injured Arteries Controls SDF-1 Mediated Neointima Formation in Apolipoprotein E Deficient Mice

E. Karshovska, A. Zernecke, G. Sevilmis, A. Millet, M. Hristov, C. D. Cohen, H. Schmid, F. Krotz, H.-Y. Sohn, V. Klauss, C. Weber, A. Schober
2007 Arteriosclerosis, Thrombosis and Vascular Biology  
Objective-Hypoxia-inducible factor (HIF)-1␣ 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)-1␣ expression. Because HIF-1␣ can be activated under normoxic conditions in smooth muscle cells (SMCs) by platelet products, we investigated the role of HIF-1␣ in SDF-1␣-mediated neointima formation after vascular injury. Methods and
more » ... injury of the left carotid artery was performed in apolipoprotein E-deficient mice. HIF-1␣ expression was increased in the media as early as 1 day after injury, predominantly in SMCs. Nuclear translocation of HIF-1␣ and colocalization with SDF-1␣ was detected in neointimal cells after 2 weeks. HIF-1␣ mRNA expression was induced at 6 hours after injury as determined by real-time RT-PCR. Inhibition of HIF-1␣ expression by local application of HIF-1␣-siRNA reduced the neointimal area by 49% and significantly decreased the neointimal SMCs content compared with control-siRNA. HIF-1␣ and SDF-1␣ expression were clearly diminished in neointimal cells of HIF-1␣-siRNA treated arteries. Conclusions-HIF-1␣ expression is directly involved in neointimal formation after vascular injury and mediates the upregulation of SDF-1␣, which may affect the stem cell-based repair of injured arteries. (Arterioscler Thromb Vasc
doi:10.1161/atvbaha.107.151050 pmid:17932320 fatcat:hu6lhvn3ofdofaajhwsgtre36e