Capillary arterialization requires the bone-marrow-derived cell (BMC)-specific expression of chemokine (C-C motif) receptor-2, but BMCs do not transdifferentiate into microvascular smooth muscle

Angiogenesis. 2009;12(4):355-63. doi: 10.1007/s10456-009-9157-1. Epub 2009 Sep 24.


Chemokine (C-C motif) receptor-2 (CCR2) regulates arteriogenesis and angiogenesis, facilitating the MCP-1-dependent recruitment of growth factor-secreting bone marrow-derived cells (BMCs). Here, we tested the hypothesis that the BMC-specific expression of CCR2 is also required for new arteriole formation via capillary arterialization. Following non-ischemic saphenous artery occlusion, we measured the following in gracilis muscles: monocyte chemotactic protein-1 (MCP-1) in wild-type (WT) C57Bl/6J mice by ELISA, and capillary arterialization in WT-WT and CCR2(-/-)-WT (donor-host) bone marrow chimeric mice, as well as BMC transdifferentiation in EGFP(+)-WT mice, by smooth muscle (SM) alpha-actin immunochemistry. MCP-1 levels were significantly elevated 1 day after occlusion in WT mice. In WT-WT mice at day 7, compared to sham controls, arterial occlusion induced a 34% increase in arteriole length density, a 46% increase in SM alpha-actin(+) vessels, and a 45% increase in the fraction of vessels coated with SM alpha-actin, indicating significant capillary arterialization. However, in CCR2(-/-)-WT mice, no differences were observed between arterial occlusion and sham surgery. In EGFP(+)-WT mice, EGFP and SM alpha-actin never colocalized. We conclude that BMC-specific CCR2 expression is required for skeletal muscle capillary arterialization following arterial occlusion; however, BMCs do not transdifferentiate into smooth muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Animals
  • Arteries
  • Arterioles / cytology
  • Arterioles / growth & development*
  • Biomarkers
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Transplantation
  • Capillaries / cytology*
  • Cell Lineage
  • Cell Transdifferentiation
  • Green Fluorescent Proteins / analysis
  • Hindlimb / blood supply
  • Laser-Doppler Flowmetry
  • Ligation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / blood supply
  • Muscle, Smooth, Vascular / cytology*
  • Radiation Chimera
  • Receptors, CCR2 / deficiency
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / physiology*


  • Actins
  • Biomarkers
  • Ccr2 protein, mouse
  • Receptors, CCR2
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins