Tie2-dependent knockout of HIF-1 impairs burn wound vascularization and homing of bone marrow-derived angiogenic cells

Kakali Sarkar, Sergio Rey, Xianjie Zhang, Raul Sebastian, Guy P. Marti, Karen Fox-Talbot, Amanda V. Cardona, Junkai Du, Yee Sun Tan, Lixin Liu, Frank Lay, Frank J. Gonzalez, John W. Harmon, Gregg L. Semenza

Research output: Contribution to journalArticlepeer-review

Abstract

Aims Hypoxia-inducible factor 1 (HIF-1) is a heterodimer composed of HIF-1α and HIF-1β 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-1α and HIF-1β, 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-1α or HIF-1β 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.

Original languageEnglish (US)
Pages (from-to)162-169
Number of pages8
JournalCardiovascular research
Volume93
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • Angiogenesis
  • Conditional knockout
  • Hypoxia
  • Wound healing

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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