CCR2+ and CX3CR1+ Bone Marrow‐Derived Cells Differentially Regulate Microvascular Remodeling in an Inflammation/Injury Model Without Transdifferentiating into Smooth Muscle

Abstract

Monocytes are generally known to regulate vascular remodeling. However, monocyte subpopulations with distinct functional roles exist, and their relative contributions to remodeling are poorly understood. Here, the relative expression of CX3CR1 and CCR2, which mark inflammatory (CCR2high/CX3CR1low) and resident (CCR2low/CX3CR1high) monocytes, was used to study the roles of these cells in regulating microvascular remodeling during injury/inflammation. Dorsal skin‐fold window chambers were implanted into wild‐type (WT) c57bl/6 mice engrafted with bone marrow‐derived cells (BMCs) from WT (control), CCR2−/−, CX3CR1−/−, or EGFP+ mice. WT control chimeras exhibited significant increases in maximum arteriolar (68%) and venular (40%) diameters from day 7 to 14. In contrast, arteriolar remodeling (‐0.8%) was completely blocked in CCR2−/− chimeras, but no change in venular remodeling was observed compared to control (37%). Interestingly, CX3CR1−/− chimeras exhibited only a partial attenuation of arteriolar (32%) and venular (14%) remodeling. EGFP+ chimeras revealed no evidence that recruited EGFP+ BMCs transdifferentiate into smooth muscle, based on examination of >800 arterioles and venules. We conclude that CCR2+ and CX3CR1+ BMCs differentially regulate microvascular remodeling during the injury/inflammation response. Because these cells do not transdifferentiate into vascular cells, it is likely that both subpopulations serve as paracrine growth factor sources. Supported by NIH HL74082.