Molecular regulation of arteriovenous endothelial cell specification.
Jennifer FangKaren K HirschiPublished in: F1000Research (2019)
The systemic circulation depends upon a highly organized, hierarchal blood vascular network that requires the successful specification of arterial and venous endothelial cells during development. This process is driven by a cascade of signaling events (including Hedgehog, vascular endothelial growth factor (VEGF), Notch, connexin (Cx), transforming growth factor-beta (TGF- β), and COUP transcription factor 2 (COUP-TFII)) to influence endothelial cell cycle status and expression of arterial or venous genes and is further regulated by hemodynamic flow. Failure of endothelial cells to properly undergo arteriovenous specification may contribute to vascular malformation and dysfunction, such as in hereditary hemorrhagic telangiectasia (HHT) and capillary malformation-arteriovenous malformation (CM-AVM) where abnormal vessel structures, such as large shunts lacking clear arteriovenous identity and function, thereby compromising peripheral blood flow. This review provides an overview of recent findings in the field of arteriovenous specification and highlights key regulators of this process.
Keyphrases
- endothelial cells
- vascular endothelial growth factor
- transforming growth factor
- cell cycle
- blood flow
- high glucose
- transcription factor
- cell fate
- cell proliferation
- epithelial mesenchymal transition
- poor prognosis
- gene expression
- high resolution
- signaling pathway
- binding protein
- dna methylation
- mass spectrometry
- dna binding