PUBLICATION
Inhibition of COX2 impairs angiogenesis and causes vascular defects in developing zebrafish embryos
- Authors
- Pillai, L., Nesari, V., Danes, D., Balakrishnan, S.
- ID
- ZDB-PUB-250403-2
- Date
- 2025
- Source
- The International journal of developmental biology : (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Dinoprostone/metabolism
- Proto-Oncogene Proteins c-akt/metabolism
- Animals
- Sulfones/pharmacology
- Cyclooxygenase 2 Inhibitors*/pharmacology
- Signal Transduction/drug effects
- Embryo, Nonmammalian*/blood supply
- Embryo, Nonmammalian*/drug effects
- Neovascularization, Physiologic*/drug effects
- Phosphatidylinositol 3-Kinases/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Cyclooxygenase 2*/metabolism
- Zebrafish*/embryology
- Zebrafish*/metabolism
- Pyridines/pharmacology
- Angiogenesis
- Gene Expression Regulation, Developmental/drug effects
- Vascular Endothelial Growth Factor Receptor-2/genetics
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- PubMed
- 40172030 Full text @ Int. J. Dev. Biol.
Citation
Pillai, L., Nesari, V., Danes, D., Balakrishnan, S. (2025) Inhibition of COX2 impairs angiogenesis and causes vascular defects in developing zebrafish embryos. The International journal of developmental biology. :.
Abstract
This study investigated the role of cyclooxygenase-2 (COX2) in angiogenesis during zebrafish embryogenesis by inhibiting COX2 activity with etoricoxib. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis confirmed the successful penetration of etoricoxib into zebrafish embryos, leading to selective inhibition of COX2 without affecting COX1 activity. COX2 inhibition caused a significant reduction in prostaglandin E2 levels throughout development. Phenotypically, treated embryos exhibited pericardial edema, bradycardia, and defective vascular development, including delays in intersegmental vessel (ISV) sprouting, incomplete dorsal longitudinal anastomotic vessel (DLAV) formation by 48 hpf, and impaired vascular networks by 72 hpf. Confocal imaging and AngioTool analysis revealed reduced vessel length, area and increased lacunarity. Molecular analysis showed significant downregulation of vascular endothelial growth factor A (vegfa), kdr, pi3k and akt transcripts, as well as reduced VEGFA, EP4 and Akt protein levels, disrupting VEGFA-PI3K-Akt signaling. Additionally, reduced expression of ephrinb and prox1 affected arterial and venous identity formation. These results demonstrate that COX2 is essential for proper angiogenesis during zebrafish development, and its inhibition leads to significant vascular defects, underscoring COX2's crucial role in regulating VEGFA-mediated angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping