Molecular Mechanisms of (R,R)ZX-5 on NO Synthesis and Its Anti-Angiogenic Effect

Abstract

(R,R)ZX-5 is a NO regulatory compound, which could significantly increase choroidal blood flow in New Zealand rabbit. The aim of this paper is to investigate the molecular mechanism of (R,R)ZX-5 promoting NO production. Besides this, we also investigated the antiangiogenic activity of (R,R)ZX-5. Analysis of Western blot showed that (R,R)ZX-5 up-regulated the expression of Akt, p-Akt (Thr473), eNOS and p-eNOS (Ser1177), down-regulated the expression of Cyclin D1 in human retinal endothelial cells and escalated the intracellular free Ca2+ concentration. Additionally, (R,R)ZX-5 inhibited the growth of blood vessels in the chick chorioallantoic membrane model. It is concluded that (R,R)ZX-5 promotes choroidal blood flow through PI3K/Akt-eNOS and Akt-Ca2+-eNOS pathways. Additionally, (R,R)ZX-5 can inhibit angiogenesis.

Keywords

• (R,R)ZX-5
• age-related macular degeneration
• choroidal neovascularization
• signal pathways
• angiogenesis