Expression of HIF-1alpha in injured arteries controls SDF-1alpha mediated neointima formation in apolipoprotein E deficient mice.
| Title: | Expression of HIF-1alpha in injured arteries controls SDF-1alpha mediated neointima formation in apolipoprotein E deficient mice. |
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| Authors: | Karshovska E; Division of Cardiology, Medizinische Poliklinik, University of Munich, Pettenkoferstrasse 8a, 80336 Munich, Germany.; Zernecke A; Sevilmis G; Millet A; Hristov M; Cohen CD; Schmid H; Krotz F; Sohn HY; Klauss V; Weber C; Schober A |
| Source: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2007 Dec; Vol. 27 (12), pp. 2540-7. Date of Electronic Publication: 2007 Oct 11. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9505803 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4636 (Electronic) Linking ISSN: 10795642 NLM ISO Abbreviation: Arterioscler Thromb Vasc Biol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins; Original Publication: Dallas, TX : American Heart Association, c1995- |
| MeSH Terms: | Apolipoproteins E/*metabolism ; Carotid Artery Injuries/*metabolism ; Carotid Artery, Common/*metabolism ; Chemokine CXCL12/*metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Tunica Intima/*metabolism ; Tunica Media/*metabolism; Apolipoproteins E/deficiency ; Apolipoproteins E/genetics ; Carotid Artery Injuries/pathology ; Carotid Artery, Common/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Myocytes, Smooth Muscle/metabolism ; RNA, Messenger/metabolism ; RNA, Small Interfering/metabolism ; Stem Cells/pathology ; Tunica Intima/pathology ; Tunica Media/pathology ; Active Transport, Cell Nucleus ; Animals ; Cell Movement ; Disease Models, Animal ; Female ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; RNA Interference ; Time Factors ; Up-Regulation |
| Abstract: | 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. |
| Substance Nomenclature: | 0 (Apolipoproteins E); 0 (Chemokine CXCL12); 0 (Cxcl12 protein, mouse); 0 (Hif1a protein, mouse); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (RNA, Messenger); 0 (RNA, Small Interfering) |
| Entry Date(s): | Date Created: 20071013 Date Completed: 20071211 Latest Revision: 20220316 |
| Update Code: | 20260130 |
| DOI: | 10.1161/ATVBAHA.107.151050 |
| PMID: | 17932320 |
| Database: | MEDLINE |
Journal Article