| First Author | Sarkar K | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 93 |
| Issue | 1 | Pages | 162-9 |
| PubMed ID | 22028336 | Mgi Jnum | J:194712 |
| Mgi Id | MGI:5474543 | Doi | 10.1093/cvr/cvr282 |
| Citation | Sarkar K, et al. (2012) Tie2-dependent knockout of HIF-1 impairs burn wound vascularization and homing of bone marrow-derived angiogenic cells. Cardiovasc Res 93(1):162-9 |
| abstractText | AIMS: Hypoxia-inducible factor 1 (HIF-1) is a heterodimer composed of HIF-1alpha and HIF-1beta subunits. HIF-1 is known to promote tissue vascularization by activating the transcription of genes encoding angiogenic factors, which bind to receptors on endothelial cells (ECs) and bone marrow-derived angiogenic cells (BMDACs). In this study, we analysed whether HIF-1 activity in the responding ECs and BMDACs is also required for cutaneous vascularization during burn wound healing. METHODS AND RESULTS: We generated mice with floxed alleles at the Hif1a or Arnt locus encoding HIF-1alpha and HIF-1beta, respectively. Expression of Cre recombinase was driven by the Tie2 gene promoter, which is expressed in ECs and bone marrow cells. Tie2Cre(+) and Tie2Cre(-) mice were subjected to burn wounds of reproducible diameter and depth. Deficiency of HIF-1alpha or HIF-1beta in Tie2-lineage cells resulted in delayed wound closure, reduced vascularization, decreased cutaneous blood flow, impaired BMDAC mobilization, and decreased BMDAC homing to burn wounds. CONCLUSION: HIF-1 activity in Tie2-lineage cells is required for the mobilization and homing of BMDACs to cutaneous burn wounds and for the vascularization of burn wound tissue. |
