Astragaloside IV regulates the HIF/VEGF/Notch signaling pathway through miRNA-210 to promote angiogenesis after ischemic stroke

• Published in: Restorative neurology and neuroscience Vol. 38; no. 3; p. 271
• Main Authors: Liang, Ce, Ni, Guang-Xiao, Shi, Xu-Liang, Jia, Lin, Wang, Ya-Li
• Format: Journal Article
• Language: English
• Published: United States Sage Publications Ltd 2020
• Subjects: Adult; Angiogenesis; Animals; Brain injury; Cell growth; Cell migration; Cell proliferation; Cell size; Cerebral blood flow; Cerebral infarction; Disease Models, Animal; Endothelial cells; Endothelial Cells - metabolism; Humans; Hypoxia; Hypoxia-Inducible Factor 1 - metabolism; Immunofluorescence; Ischemia; Ischemic Stroke - metabolism; Kinases; Male; MicroRNAs - metabolism; miRNA; Neovascularization, Pathologic - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Notch - metabolism; Saponins - pharmacology; Signal transduction; Signal Transduction - drug effects; Stroke; Triphenyltetrazolium chloride; Triterpenes - pharmacology; Umbilical vein; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascularization; Astragaloside IV; HIF/VEGF/Notch signaling pathway; miRNA-210; angiogenesis; ischemic stroke
• ISSN: 0922-6028; 1878-3627; 1878-3627
• DOI: 10.3233/RNN-201001

Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalusmembranaceus. Studies have shown that AS-IV stimulates angiogenesis, including cell proliferation, migration, and neovascularization. However, the relevant mechanism remains unclear. This study aims to investigate whether AS-IV activates the HIF/VEGF/Notch signaling pathway through miRNA-210 to promote angiogenesisafter ischemic stroke. The present study established a rat model of middle cerebral artery occlusion (MCAO) and cultured human umbilical vein endothelial cells (HUVECs) under hypoxic conditions in vitro to investigate the role of AS-IV in promoting angiogenesis and reveal its underlying mechanism. Through in vivo studies, the area of cerebral infarction was determined by 2,3,5-triPhenyltetrazolium chloride (TTC) staining. Immunofluorescence staining and RT-qPCR were used to detect the expression changes of miRNA-210 and ephrinA3 in the ischemic cortex after ischemia. Through in vitro studies, cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Subsequently, angiogenesis experiments were performed to observe the angiogenic ability. Results revealed that AS-IV significantly reduced infarct size, promoted cell proliferation and ductal formation, and inhibited the expression of the target gene ephrinA3 by increasing the expression of miRNA-210 and inducing activation of the HIF-VEGF-Notch signaling pathway. AS-IV promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA-210.