PUBLICATION
CXCR3-CXCL11 Signaling Restricts Angiogenesis and Promotes Pericyte Recruitment
- Authors
- Lee, J., Goeckel, M.E., Levitas, A., Colijn, S., Shin, J., Hindes, A., Mun, G., Burton, Z., Chintalapati, B., Yin, Y., Abello, J., Solnica-Krezel, L., Stratman, A.
- ID
- ZDB-PUB-241003-12
- Date
- 2024
- Source
- Arteriosclerosis, Thrombosis, and Vascular Biology 44(12): 2577-2595 (Journal)
- Registered Authors
- Abello, Javier, Colijn, Sarah, Goeckel, Megan, Hindes, Anna, Levitas, Alli, Shin, Jimann, Solnica-Krezel, Lilianna, Stratman, Amber, Yin, Ying
- Keywords
- endothelial cells, gain-of-function mutation, hemodynamics, pericytes, zebra fish
- MeSH Terms
-
- Cell Movement
- Receptors, CXCR3*/genetics
- Receptors, CXCR3*/metabolism
- Zebrafish*
- Chemokine CXCL11*/genetics
- Chemokine CXCL11*/metabolism
- Animals, Genetically Modified
- Angiogenesis
- Regional Blood Flow
- Cells, Cultured
- Endothelial Cells/metabolism
- Cell Communication
- Humans
- Signal Transduction*
- Animals
- Mutation
- Neovascularization, Physiologic*
- Coculture Techniques
- Pericytes*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Human Umbilical Vein Endothelial Cells/metabolism
- Phenotype
- PubMed
- 39360413 Full text @ Arterio., Thromb., and Vas. Bio.
Citation
Lee, J., Goeckel, M.E., Levitas, A., Colijn, S., Shin, J., Hindes, A., Mun, G., Burton, Z., Chintalapati, B., Yin, Y., Abello, J., Solnica-Krezel, L., Stratman, A. (2024) CXCR3-CXCL11 Signaling Restricts Angiogenesis and Promotes Pericyte Recruitment. Arteriosclerosis, Thrombosis, and Vascular Biology. 44(12):2577-2595.
Abstract
Background Endothelial cell (EC)-pericyte interactions are known to remodel in response to hemodynamic forces; yet there is a lack of mechanistic understanding of the signaling pathways that underlie these events. Here, we have identified a novel signaling network regulated by blood flow in ECs-the chemokine receptor CXCR3 (CXC motif chemokine receptor 3) and one of its ligands, CXCL11 (CXC motif chemokine ligand 11)-that delimits EC angiogenic potential and promotes pericyte recruitment to ECs during development.
Methods We investigated the role of CXCR3 on vascular development using both 2- and 3-dimensional in vitro assays, to study EC-pericyte interactions and EC behavioral responses to blood flow. Additionally, genetic mutants and pharmacological modulators were used in zebra fish in vivo to study the impacts of CXCR3 loss and gain of function on vascular development.
Results In vitro modeling of EC-pericyte interactions demonstrates that suppression of EC-specific CXCR3 signaling leads to loss of pericyte association with EC tubes. In vivo, phenotypic defects are particularly noted in the cranial vasculature, where we see a loss of pericyte association with ECs and expansion of the vasculature in zebra fish treated with the Cxcr3 inhibitor AMG487 or in homozygous cxcr3.1/3.2/3.3 triple mutants. We also demonstrate that CXCR3-deficient ECs are more elongated, move more slowly, and have impaired EC-EC junctions compared with their control counterparts.
Conclusions Our results suggest that CXCR3 signaling in ECs helps promote vascular stabilization events during development by preventing EC overgrowth and promoting pericyte recruitment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping