Hypoxia and upregulation of hypoxia-inducible factor 1{alpha} stimulate venous thrombus recanalization

Angiogenic factors are expressed within thrombus during resolution, but the primary stimulus for neovascularization is unknown. Our aims were to determine whether (1) hypoxia and hypoxia-inducible factor 1α (HIF1α) are induced in resolving thrombus, (2) this stimulates angiogenic factor production,...

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Veröffentlicht in:	Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2010-12, Vol.30 (12), p.2443-2451
Hauptverfasser:	Evans, Colin Edward, Humphries, Julia, Mattock, Katherine, Waltham, Matthew, Wadoodi, Ashar, Saha, Prakash, Modarai, Bijan, Maxwell, Patrick H, Maxwell, Patrick J, Smith, Alberto
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Cell Hypoxia Cytokines - metabolism Disease Models, Animal Enzyme Inhibitors - pharmacology Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Macrophages - immunology Male Mice Mice, Inbred BALB C Mimosine - pharmacology Neovascularization, Physiologic - drug effects Neutrophil Infiltration Neutrophils - immunology Oxygen - metabolism Procollagen-Proline Dioxygenase - antagonists & inhibitors Procollagen-Proline Dioxygenase - metabolism Time Factors Up-Regulation Vascular Endothelial Growth Factor A - metabolism Vascular Endothelial Growth Factor Receptor-1 - metabolism Vena Cava, Inferior - drug effects Vena Cava, Inferior - immunology Vena Cava, Inferior - metabolism Venous Thrombosis - immunology Venous Thrombosis - metabolism Venous Thrombosis - physiopathology
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Zusammenfassung:	Angiogenic factors are expressed within thrombus during resolution, but the primary stimulus for neovascularization is unknown. Our aims were to determine whether (1) hypoxia and hypoxia-inducible factor 1α (HIF1α) are induced in resolving thrombus, (2) this stimulates angiogenic factor production, and (3) upregulating HIF1α enhances thrombus resolution and vein recanalization. Oxygen tension in the thrombus was negatively correlated with HIF1α levels (Spearman correlation [RS] = -0.77, P
ISSN:	1524-4636
DOI:	10.1161/ATVBAHA.110.215038