Bone marrow-derived cell-specific chemokine (C-C motif) receptor-2 expression is required for arteriolar remodeling

Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1794-801. doi: 10.1161/ATVBAHA.109.194019. Epub 2009 Sep 4.


Objective: Bone marrow-derived cells (BMCs) and inflammatory chemokine receptors regulate arteriogenesis and angiogenesis. Here, we tested whether arteriolar remodeling in response to an inflammatory stimulus is dependent on BMC-specific chemokine (C-C motif) receptor 2 (CCR2) expression and whether this response involves BMC transdifferentiation into smooth muscle.

Methods and results: Dorsal skinfold window chambers were implanted into C57Bl/6 wild-type (WT) mice, as well as the following bone marrow chimeras (donor-host): WT-WT, CCR2(-/-)-WT, WT-CCR2(-/-), and EGFP(+)-WT. One day after implantation, tissue MCP-1 levels rose from "undetectable" to 463 pg/mg, and the number of EGFP(+) cells increased more than 4-fold, indicating marked inflammation. A 66% (28 microm) increase in maximum arteriolar diameter was observed over 7 days in WT-WT mice. This arteriolar remodeling response was completely abolished in CCR2(-/-)-WT mice but largely rescued in WT-CCR2(-/-) mice. EGFP(+) BMCs were numerous throughout the tissue, but we found no evidence that EGFP(+) BMCs transdifferentiate into smooth muscle, based on examination of >800 arterioles and venules.

Conclusions: BMC-specific CCR2 expression is required for injury/inflammation-associated arteriolar remodeling, but this response is not characterized by the differentiation of BMCs into smooth muscle.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Arterioles / physiology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Transplantation
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression Regulation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Neovascularization, Physiologic / physiology
  • Probability
  • Random Allocation
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism*
  • Regeneration / physiology*


  • Receptors, CCR2