Abscisic Acid/Dormin, a Plant Hormone that Inhibits Angiogenesis in vitro and Neovascular Growth in vivo

Abstract

Vessel development and regeneration by angiogenesis is critical for adequate oxygen and nutrient delivery to every organ in the body. However, the concept of anti‐angiogenesis therapy has previously been proposed due to the important role of blood vessels in solid tumor growth and dissemination. Non‐neoplastic disorders associated with numerous proliferative diseases (e.g. diabetes or chronic inflammation) also are promoted by pathological angiogenesis that leads to blinding diseases. Current anti‐angiogenic treatments are based on the use of synthetic drugs, many of which, not only cause serious side effects without correcting the underlying pathology, but also have an unfavorable cost to benefit ratio. The objective of this study is to explore the anti‐angiogenic potential of abscisic acid (ABA), a natural plant hormone that inhibits germination from occurring when the environmental conditions are not favorable and contributes to the acquisition of stress tolerance. Using a fibrin beads‐based sprouting assay, we show that ABA effectively inhibits in a dose‐dependent manner, migration, growth and expansion of endothelial tubes without affecting cell viability. In the in vivo model of postnatal retinal angiogenesis, administration of ABA affects neither the differentiation and normal development of the retinal vasculature nor the growth of the animals although it incidentally increases fetal hyaloid vessel persistence. In the mouse model of oxygen‐induced retinopathy (OIR) characterized by a hyperoxia‐induced vaso‐obliteration phase and a subsequent ischemia‐induced neovascular growth, administration of ABA reduces aberrant growth of retinal vessels during the ischemic phase of OIR without altering the normal vascularization of the retina. Thus, as a natural vascular stabilization signal restricting neovascular growth, ABA is an anti‐angiogenic molecule with potential translational implications in vascular diseases of the eye.