PUBLICATION
Dissecting VEGF-induced acute versus chronic vascular hyperpermeability: Essential roles of dimethylarginine dimethylaminohydrolase-1
- Authors
- Wang, Y., Angom, R.S., Kulkarni, T.A., Hoeppner, L.H., Pal, K., Wang, E., Tam, A., Valiunas, R.A., Dutta, S.K., Ji, B., Jarzebska, N., Chen, Y., Rodionov, R.N., Mukhopadhyay, D.
- ID
- ZDB-PUB-211028-3
- Date
- 2021
- Source
- iScience 24: 103189 (Journal)
- Registered Authors
- Angom, Ramcharan Singh, Dutta, Shamit, Mukhopadhyay, Debabrata, Wang, Enfeng, Wang, Ying
- Keywords
- Cardiovascular medicine, Molecular genetics
- MeSH Terms
- none
- PubMed
- 34703990 Full text @ iScience
Citation
Wang, Y., Angom, R.S., Kulkarni, T.A., Hoeppner, L.H., Pal, K., Wang, E., Tam, A., Valiunas, R.A., Dutta, S.K., Ji, B., Jarzebska, N., Chen, Y., Rodionov, R.N., Mukhopadhyay, D. (2021) Dissecting VEGF-induced acute versus chronic vascular hyperpermeability: Essential roles of dimethylarginine dimethylaminohydrolase-1. iScience. 24:103189.
Abstract
Vascular endothelial cell growth factor (VEGF) is a key regulator of vascular permeability. Herein we aim to understand how acute and chronic exposures of VEGF induce different levels of vascular permeability. We demonstrate that chronic VEGF exposure leads to decreased phosphorylation of VEGFR2 and c-Src as well as steady increases of nitric oxide (NO) as compared to that of acute exposure. Utilizing heat-inducible VEGF transgenic zebrafish (Danio rerio) and establishing an algorithm incorporating segmentation techniques for quantification, we monitored acute and chronic VEGF-induced vascular hyperpermeability in real time. Importantly, dimethylarginine dimethylaminohydrolase-1 (DDAH1), an enzyme essential for NO generation, was shown to play essential roles in both acute and chronic vascular permeability in cultured human cells, zebrafish model, and Miles assay. Taken together, our data reveal acute and chronic VEGF exposures induce divergent signaling pathways and identify DDAH1 as a critical player and potentially a therapeutic target of vascular hyperpermeability-mediated pathogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping