Targeting expression of adenosine receptors during hypoxia induced angiogenesis – A study using zebrafish model

Publication date: March 2018 Source:Biomedicine & Pharmacotherapy, Volume 99 Author(s): Navina Panneerselvan, Malathi Ragunathan Hypoxia is known to be a major player during pathological angiogenesis and adenosine as a negative feedback signaling to maintain oxygen delivery in pathological ischemic condition. We mimicked hypoxic condition and studied angiogenesis by inducing adenosine receptors using forskolin, a plant compound and NECA analogue of adenosine using zebrafish model. Vascular endothelial growth factor (VEGF) is known to play a key role during pathological angiogenesis and regulated by the factors HIF1a under hypoxic condition and recently Notch is proposed to play a negative feedback loop mechanism along with VEGF signaling but the role of adenosine receptor during the process is not known. We evaluated the mRNA expression of adenosine receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A, VEGF R2, NRP1a, NOTCH 1a and DLL4 and the phenotypic variations of zebrafish embryos when treated with DAPT, γ-secretase inhibitor of Notch in addition to treating the embryos with SU5416, a VEGF receptor inhibitor. Upregulation of adenosine receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A, VEGF R2, NRP1a, NOTCH1a and DLL4 was observed embryos were when treated with forskolin and NECA could possibly mimic hypoxic condition. Hatching and heart rate also increased with NECA and forskolin. SU5416 showed decreases in blood vessel formation and decreased adenosine receptors...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research