Loss of endothelial-ARNT in adult mice contributes to dampened circulating proangiogenic cells and delayed wound healing

We report here that conditional inactivation of hypoxia-inducible factor’s (HIF) transcriptional activity in the endothelium of adult mice (ArntiEC 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 ArntiEC 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 ArntiEC 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.
Source: Vascular Medicine - Category: Internal Medicine Authors: Tags: Original Articles Source Type: research