Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009;12(4):355-63.
doi: 10.1007/s10456-009-9157-1. Epub 2009 Sep 24.

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

Affiliations
Free PMC article

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

Meghan M Nickerson et al. Angiogenesis. .
Free PMC article

Abstract

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.

Figures

Fig. 1
Fig. 1
Animal model characterization. a Line graph of laser doppler perfusion imaging (LDPI) ratios for “non-ischemic” saphenous (n = 3) and “ischemic” (n = 3) femoral artery occlusion models in C57Bl/6J mice. Values are mean ± standard deviation (SD). * Significantly different than non-ischemic at same time point (P <0.05). b Bar graph of MCP-1 expression levels in WT gracilis muscle after non-ischemic saphenous artery occlusion at days 0, 1, 4, and 7 (n = 4 per group). Values are mean ± SD. * Significantly different than all other time points (P < 0.05)
Fig. 2
Fig. 2
The deletion of CCR2 from BMCs inhibits capillary arterialization as assessed in whole-mounts. a, b Confocal images of SM α-actin labeled gracilis muscles exposed to arterial occlusion from WT–WT (a) and CCR2−/−–WT (b) mice at day 7. Arrows denote long extensions of SM α-actin expression along capillaries running parallel to the muscle fiber direction. c Bar graph of arteriole length density for WT–WT (n = 5) and CCR2−/−–WT (n = 5) mice. * Significantly different than all other groups (P <0.05)
Fig. 3
Fig. 3
The deletion of CCR2 expression from BMCs inhibits capillary arterialization as assessed in cross-sections. a Confocal images of cross-sectioned gracilis muscles from WT–WT and CCR2−/−–WT mice at 7 days after arterial occlusion. Arterioles and venules are labeled with SM α-actin, while all small microvessels are labeled with BS-I lectin. Co-localization of BS-I lectin and SM α-actin is shown in the merge panel. b Bar graph of SM α-actin+ profiles per muscle fiber for WT–WT (n = 5) and CCR2−/−–WT (n = 5) mice. * Significantly different than WT–WT arterial occlusion group (P < 0.05). c Bar graph of the ratio of SM α-actin+ profiles to BS-I lectin profiles. * Significantly different than WT–WT saphenous occlusion group (P <0.05)
Fig. 4
Fig. 4
Representative confocal images of EGFP+ BMCs in SM α-actin immunolabeled gracilis muscle at 7 days after “non-ischemic” saphenous artery occlusion. The colocalization of EGFP with SM α-actin was never observed in EGFP+–WT bone marrow chimeric mice (n = 3)

Similar articles

See all similar articles

Cited by 13 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback