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Arteriolar and venular remodeling are differentially regulated by bone marrow-derived cell-specific CX3CR1 and CCR2
Joshua K Meisner1, Ji Song, Richard J Price
1Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
Insights
Bone marrow-derived cell chemokine receptors CCR2 and CX3CR1 differentially regulate microvascular remodeling. CCR2 and CX3CR1 control arteriole remodeling, while CX3CR1 specifically impacts venule remodeling.
Area of Science:
- Immunology
- Vascular Biology
- Cell Biology
Background:
- Chemokine receptors CCR2 and CX3CR1 mediate monocyte recruitment.
- Monocyte subpopulations differentially influence vascular remodeling in atherosclerosis.
- Understanding these roles is key to developing targeted therapies.
Purpose of the Study:
- To investigate the distinct roles of bone marrow-derived cell (BMC)-specific CCR2 and CX3CR1 in venular and arteriolar remodeling.
- To test the hypothesis that these receptors differentially control microvascular remodeling.
Main Methods:
- Intravital microscopy was used to observe lumenal remodeling in venules and arterioles.
- Mice with CCR2 or CX3CR1 deficient BMCs were studied after dorsal skinfold window chamber implantation.
- Comparisons were made to wild-type (WT) controls.
Main Results:
- Arteriolar remodeling was abolished in mice lacking CCR2 or CX3CR1 in BMCs.
- Loss of CX3CR1 in BMCs, but not CCR2, significantly reduced small venule remodeling compared to WT.
- These findings highlight differential regulation of microvascular remodeling by BMC-expressed chemokine receptors.
Conclusions:
- BMC-expressed CCR2 and CX3CR1 differentially regulate microvascular remodeling.
- Both receptors are crucial for arteriole growth.
- Only BMC-derived CX3CR1 influences small venule growth, suggesting distinct roles in microvascular adaptation.
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.
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