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.
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.
Department of Biomedical Engineering, University of Virginia, UVA Health System, Charlottesville, VA 22908, USA.
Meghan M
MM
Nickerson
Caitlin W
CW
Burke
Joshua K
JK
Meisner
Casey W
CW
Shuptrine
Ji
J
Song
Richard J
RJ
Price
D000199:Actins / Q000032:analysis; D000818:Animals; D001158:Arteries; D001160:Arterioles / Q000166:cytology / Q000254:growth & development*; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002196:Capillaries / Q000166:cytology*; D019070:Cell Lineage; D054338:Cell Transdifferentiation; D049452:Green Fluorescent Proteins / Q000032:analysis; D006614:Hindlimb / Q000098:blood supply; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011828:Radiation Chimera; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000199:Actins; D015415:Biomarkers; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins