Arteriogenesis in murine adipose tissue is contingent on CD68+ /CD206+ macrophages

Microcirculation. 2017 May;24(4):10.1111/micc.12341. doi: 10.1111/micc.12341.


Objective: The surgical transfer of skin, fat, and/or muscle from a donor site to a recipient site within the same patient is a widely performed procedure in reconstructive surgeries. A surgical pretreatment strategy that is intended to increase perfusion in the flap, termed "flap delay," is a commonly employed technique by plastic surgeons prior to flap transplantation. Here, we explored whether CD68+ /CD206+ macrophages are required for arteriogenesis within the flap by performing gain-of-function and loss-of-function studies in a previously published flap delay murine model.

Methods and results: Local injection of M2-polarized macrophages into the flap resulted in an increase in collateral vessel diameter. Application of a thin biomaterial film loaded with a pharmacological agent (FTY720), which has been previously shown to recruit CD68+ /CD206+ macrophages to remodeling tissue, increased CD68+ /CD206+ cell recruitment and collateral vessel enlargement. Conversely, when local macrophage populations were depleted within the inguinal fat pad via clodronate liposome delivery, we observed fewer CD68+ cells accompanied by diminished collateral vessel enlargement.

Conclusions: Our study underscores the importance of macrophages during microvascular adaptations that are induced by flap delay. These studies suggest a mechanism for a translatable therapeutic target that may be used to enhance the clinical flap delay procedure.

Keywords: adipose; arteriogenesis; collateral vessel; macrophage.

MeSH terms

  • Adipose Tissue / blood supply*
  • Animals
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Arteries / cytology
  • Arteries / drug effects
  • Arteries / growth & development*
  • Cell Movement / drug effects
  • Fingolimod Hydrochloride / administration & dosage
  • Fingolimod Hydrochloride / pharmacology
  • Lectins, C-Type / analysis
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / physiology*
  • Mannose Receptor
  • Mannose-Binding Lectins / analysis
  • Mice
  • Neovascularization, Physiologic / physiology*
  • Receptors, Cell Surface / analysis
  • Surgical Flaps / blood supply*
  • Surgical Flaps / transplantation


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 protein, mouse
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Fingolimod Hydrochloride