Myeloid ALX/FPR2 regulates vascularization following tissue injury

Brian E. Sansbury, Xiaofeng Li, Blenda Wong, Andreas Patsalos, Andreas Patsalos, Nikolas Giannakis, Michael J. Zhang, Laszlo Nagy, Matthew Spite

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Ischemic injury initiates a sterile inflammatory response that ultimately participates in the repair and recovery of tissue perfusion. Macrophages are required for perfusion recovery during ischemia, in part because they produce growth factors that aid in vascular remodeling. The input signals governing this pro-revascularization phenotype remain of interest. Here we found that hindlimb ischemia increases levels of resolvin D1 (RvD1), an inflammationresolving lipid mediator that targets macrophages via its receptor, ALX/FPR2. Exogenous RvD1 enhances perfusion recovery during ischemia, and mice deficient in Alx/Fpr2 have an endogenous defect in this process. Mechanistically, RNA sequencing revealed that RvD1 induces a transcriptional program in macrophages characteristic of a pro-revascularization phenotype. Vascularization of ischemic skeletal muscle, as well as cutaneous wounds, is impaired in mice with myeloid-specific deficiency of Alx/Fpr2, and this is associated with altered expression of pro-revascularization genes in skeletal muscle and macrophages isolated from skeletal muscle. Collectively, these results uncover a role of ALX/FPR2 in revascularization that may be amenable to therapeutic targeting in diseases associated with altered tissue perfusion and repair.

Original languageEnglish (US)
Pages (from-to)14354-14364
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - Jun 23 2020


  • Ischemia
  • Macrophages
  • Resolvins

ASJC Scopus subject areas

  • General


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