Abstract

As abnormal angiogenesis is associated with exacerbation of various diseases, precise control over angiogenesis is imperative. Vascular endothelial growth factor (VEGF), the most well-known angiogenic factor, binds to VEGF receptor (VEGFR), activates various signaling pathways, and mediates angiogenesis. Therefore, blocking the VEGF-induced angiogenic response-related signaling pathways may alleviate various disease symptoms through inhibition of angiogenesis. Ulmus davidiana is a safe natural product that has been traditionally consumed, but its effects on endothelial cells (ECs) and the underlying mechanism of action are unclear. In the present study, we focused on the effect of a 60% edible ethanolic extract of U. davidiana (U60E) on angiogenesis. U60E inhibited the VEGF-mediated proliferation, tube formation, and migration ability of ECs. Mechanistically, U60E inhibited endothelial nitric oxide synthase activation and nitric oxide production by blocking the protein kinase B signaling pathway activated by VEGF and consequently inhibiting proliferation, tube formation, and migration of ECs. These results suggest that U60E could be a potential and safe therapeutic agent capable of suppressing proangiogenic diseases by inhibiting VEGF-induced angiogenesis.

Highlights

  • Angiogenesis is the process of forming new blood vessels from existing ones

  • We demonstrate that U60E prevented the proliferation, tube formation, and migration abilities of endothelial cells (ECs) by blocking the Vascular endothelial growth factor (VEGF)-induced as phosphoinositide 3-kinase/protein kinase B (Akt)/endothelial nitric oxide synthase/nitric oxide (NO) pathway

  • U. davidiana was previously shown to reduce NO production in macrophages and microglia [29,30,31]; we investigated how U60E affects the activity of endothelial nitric oxide synthase (eNOS), which induces NO production in ECs

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Summary

Introduction

Angiogenesis is the process of forming new blood vessels from existing ones. As any dysregulation in angiogenesis is associated with various diseases, this process requires elaborate control [1,2,3]. Uncontrolled angiogenesis around the tumor and in the retina may worsen cancer and retinopathy, respectively. As tumor cells need blood vessels to receive nutrients and oxygen, angiogenesis is common around tumor cells and facilitates cancer growth and metastasis [3]. Abnormal angiogenesis is common in retinopathy such as diabetic retinopathy (DR) and retinopathy of prematurity (ROP), which may lead to blindness owing to the dysfunction of the retina [4,5]. Preventing abnormal angiogenesis under disease conditions such as cancer or retinopathy may offer potential therapeutic benefits

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