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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1794.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Bone Marrow–Derived Cell-Specific Chemokine (C-C Motif) Receptor-2 Expression is Required for Arteriolar Remodeling

Meghan M. Nickerson; Ji Song; Joshua K. Meisner; Sameer Bajikar; Caitlin W. Burke; Casey W. Shuptrine; Gary K. Owens; Thomas C. Skalak; Richard J. Price

From the Department of Biomedical Engineering (M.M.N., J.S., J.K.M., S.B., C.W.B., C.W.S., T.C.S., R.J.P.), the Department of Molecular Physiology and Biological Physics (G.K.O.), and the Robert M. Berne Cardiovascular Research Center (G.K.O., R.J.P.), University of Virginia, Charlottesville.

Correspondence to Richard J. Price, PhD, Associate Professor, Department of Biomedical Engineering, University of Virginia, Box 800759, UVA Health System, Charlottesville, VA 22908. E-mail rprice{at}virginia.edu

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 463pg/mg, and the number of EGFP⁺ cells increased more than 4-fold, indicating marked inflammation. A 66% (28 µm) 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.

Dorsal skinfold window chamber implantation elicits inflammation, arteriolar remodeling, and bone marrow–derived cell recruitment without transdifferentiation into smooth muscle. In this model, both arteriolar remodeling and monocyte/macrophage recruitment are dependent on bone marrow–derived cell-specific CCR2 expression.

Key Words: microcirculation • arteriolar remodeling • CCR2 • MCP-1 • bone marrow derived cells