Loss of endothelial-ARNT in adult mice contributes to dampened circulating proangiogenic cells and delayed wound healing.
Autor: | Han Y; Case Cardiovascular Research Institute and University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University School of Medicine, Cleveland, OH, USA University of Rochester, School of Medicine and Dentistry, Rochester, NY, USA., Tao J; Case Cardiovascular Research Institute and University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Gomer A; Case Cardiovascular Research Institute and University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Ramirez-Bergeron DL; Case Cardiovascular Research Institute and University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University School of Medicine, Cleveland, OH, USA dlr36@case.edu. |
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Jazyk: | angličtina |
Zdroj: | Vascular medicine (London, England) [Vasc Med] 2014 Dec; Vol. 19 (6), pp. 429-41. Date of Electronic Publication: 2014 Nov 14. |
DOI: | 10.1177/1358863X14559588 |
Abstrakt: | The recruitment and homing of circulating bone marrow-derived cells include endothelial progenitor cells (EPCs) that are critical to neovascularization and tissue regeneration of various vascular pathologies. We report here that conditional inactivation of hypoxia-inducible factor's (HIF) transcriptional activity in the endothelium of adult mice (Arnt(ΔiEC) mice) results in a disturbance of infiltrating cells, a hallmark of neoangiogenesis, during the early phases of wound healing. Cutaneous biopsy punches show distinct migration of CD31(+) cells into wounds of control mice by 36 hours. However, a significant decline in numbers of infiltrating cells with immature vascular markers, as well as decreased transcript levels of genes associated with their expression and recruitment, were identified in wounds of Arnt(ΔiEC) mice. Matrigel plug assays further confirmed neoangiogenic deficiencies alongside a reduction in numbers of proangiogenic progenitor cells from bone marrow and peripheral blood samples of recombinant vascular endothelial growth factor-treated Arnt(ΔiEC) mice. In addition to HIF's autocrine requirements in endothelial cells, our data implicate that extrinsic microenvironmental cues provided by endothelial HIF are pivotal for early migration of proangiogenic cells, including those involved in wound healing. (© The Author(s) 2014.) |
Databáze: | MEDLINE |
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