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


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.
Nickerson
Meghan M
MM
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
Song
Ji
J
Meisner
Joshua K
JK
Bajikar
Sameer
S
Burke
Caitlin W
CW
Shuptrine
Casey W
CW
Owens
Gary K
GK
Skalak
Thomas C
TC
Price
Richard J
RJ
D000704:Analysis of Variance; D000818:Animals; D001160:Arterioles / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology; D011336:Probability; D011897:Random Allocation; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*
D054390:Receptors, CCR2