PUBLICATION
Oxidative pentose phosphate pathway controls vascular mural cell coverage by regulating extracellular matrix composition
- Authors
- Facchinello, N., Astone, M., Audano, M., Oberkersch, R.E., Spizzotin, M., Calura, E., Marques, M., Crisan, M., Mitro, N., Santoro, M.M.
- ID
- ZDB-PUB-220202-33
- Date
- 2022
- Source
- Nature metabolism 4: 123-140 (Journal)
- Registered Authors
- Astone, Matteo, Facchinello, Nicola, Santoro, Massimo
- Keywords
- none
- MeSH Terms
-
- Animals
- Biomarkers
- Blood Vessels/cytology*
- Blood Vessels/metabolism*
- Elastin/biosynthesis
- Elastin/genetics
- Endothelial Cells/metabolism
- Endothelial Cells/ultrastructure
- Extracellular Matrix/metabolism*
- Gene Expression
- Genes, Reporter
- Glucose/metabolism
- Hemodynamics
- Mice
- Mice, Knockout
- Models, Biological
- Oxidative Phosphorylation*
- Oxidative Stress
- Pentose Phosphate Pathway*
- Pentosephosphates/metabolism
- Zebrafish
- PubMed
- 35102339 Full text @ Nat Metab
Citation
Facchinello, N., Astone, M., Audano, M., Oberkersch, R.E., Spizzotin, M., Calura, E., Marques, M., Crisan, M., Mitro, N., Santoro, M.M. (2022) Oxidative pentose phosphate pathway controls vascular mural cell coverage by regulating extracellular matrix composition. Nature metabolism. 4:123-140.
Abstract
Vascular mural cells (vMCs) play an essential role in the development and maturation of the vasculature by promoting vessel stabilization through their interactions with endothelial cells. Whether endothelial metabolism influences mural cell recruitment and differentiation is unknown. Here, we show that the oxidative pentose phosphate pathway (oxPPP) in endothelial cells is required for establishing vMC coverage of the dorsal aorta during early vertebrate development in zebrafish and mice. We demonstrate that laminar shear stress and blood flow maintain oxPPP activity, which in turn, promotes elastin expression in blood vessels through production of ribose-5-phosphate. Elastin is both necessary and sufficient to drive vMC recruitment and maintenance when the oxPPP is active. In summary, our work demonstrates that endothelial cell metabolism regulates blood vessel maturation by controlling vascular matrix composition and vMC recruitment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping