Abstract
The chemokine receptors CCR2 and CX3CR1 are critical for the recruitment of “inflammatory” and “resident” monocytes, respectively, subpopulations that differentially affect vascular remodeling in atherosclerosis. Here, we tested the hypothesis that bone marrow-derived cell (BMC)-specific CCR2 and CX3CR1 differentially control venular and arteriolar remodeling. Venular and arteriolar lumenal remodeling were observed by intravital microscopy in mice with either CCR2 or CX3CR1 deficient BMCs after implantation of a dorsal skinfold window chamber, a model in which arterioles and venules lumenally enlarge in wild-type (WT) mice. Arteriolar remodeling was abolished in mice with either CCR2 or CX3CR1-deficient BMCs. In contrast, the loss of CX3CR1 from BMCs, but not CCR2, significantly reduced small venule remodeling compared to WT controls. We conclude that microvascular remodeling is differentially regulated by BMC-expressed chemokine receptors. Both CCR2 and CX3CR1 regulate arteriole growth; however, only BMC-expressed CX3CR1 impacts small venule growth. These findings may provide a basis for additional investigations aimed at determining how patterns of monocyte subpopulation recruitment spatially influence microvascular remodeling.
Highlights
Bone marrow derived cells (BMCs), and monocytes in particular, regulate vascular remodeling
We tested this hypothesis by examining the remodeling of arterioles and venules through time in dorsal skinfold window chambers (DSFWCs) implanted on chimeric mice that were generated by transplanting bone marrow from either CCR22/2 or CX3CR12/2 donors into wild type (WT) hosts
The major finding from this study is that the influence of BMCs on microvascular remodeling is surprisingly complex and dependent upon multiple factors, including chemokine receptor expression (i.e. CCR2 and CX3CR1), the type of microvessel being considered, and initial microvessel diameter
Summary
Bone marrow derived cells (BMCs), and monocytes in particular, regulate vascular remodeling. In the context of another vascular remodeling scenario (i.e. atherosclerosis), ‘‘inflammatory’’ and ‘‘resident’’ monocytes exhibit different functional roles in remodeling [10,11] Given this background, as well as the recent emphasis on both CCR2mediated recruitment through arterial signaling during arteriogenesis [12,13] and CX3CR1-mediated recruitment through venous patrolling [7], we hypothesize that monocytes that are recruited to tissue via CCR2 and CX3CR1 play differential roles in arteriolar and venular microvascular remodeling [14]. We tested this hypothesis by examining the remodeling of arterioles and venules through time in dorsal skinfold window chambers (DSFWCs) implanted on chimeric mice that were generated by transplanting bone marrow from either CCR22/2 or CX3CR12/2 donors into wild type (WT) hosts
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