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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 Nickerson MM; Burke CW; Meisner JK; Shuptrine CW; Song J; Price RJAngiogenesis 2009[]; 12 (4): 355-63Chemokine (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.|Actins/analysis[MESH]|Animals[MESH]|Arteries[MESH]|Arterioles/cytology/*growth & development[MESH]|Biomarkers[MESH]|Bone Marrow Cells/cytology/*metabolism[MESH]|Bone Marrow Transplantation[MESH]|Capillaries/*cytology[MESH]|Cell Lineage[MESH]|Cell Transdifferentiation[MESH]|Green Fluorescent Proteins/analysis[MESH]|Hindlimb/blood supply[MESH]|Laser-Doppler Flowmetry[MESH]|Ligation[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Mice, Knockout[MESH]|Muscle, Skeletal/blood supply[MESH]|Muscle, Smooth, Vascular/*cytology[MESH]|Radiation Chimera[MESH]|Receptors, CCR2/deficiency/genetics/*physiology[MESH] |
