TY  - JOUR
TI  - Inhibition of COX2 impairs angiogenesis and causes vascular defects in developing zebrafish embryos
AU  - Pillai, Lakshmi
AU  - Nesari, Vishakha
AU  - Danes, Dhanush
AU  - Balakrishnan, Suresh
T2  - The International Journal of Developmental Biology
AB  - 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.
PY  - 2025
DO  - 10.1387/ijdb.240222sb
VL  - In Press
IS  - In Press
SP  - 222
EP  - 222
J2  - Int. J. Dev. Biol.
LA  - en
SN  - 0214-6282
SN  - 1696-3547
UR  - https://ijdb.ehu.eus/article/240222sb
Y2  - 2025/04/05/13:08:22
ER  -