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

Liang, Ce; Ni, Guangxiao; Shi, Xuliang; Jia, Lin; Wang, Yali

doi:10.3233/rnn-201001

Cited by 30 publications

(21 citation statements)

References 28 publications

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“…Moreover, the results indicated that AS-IV alleviated hypoxia-induced pulmonary vascular remodeling in vitro and in vivo. Together with the results of a previous study (41), the present study suggested that the effects of AS-IV might be mediated via downregulation of Jagged-1/Notch-3/Hes-5 expression. Therefore, the present study indicated that AS-IV might display important therapeutic functions as part of the Radix Astragali Mongolici extract for the prevention and treatment of cardiovascular disorders, such as PAH.…”

Section: Discussionsupporting

confidence: 87%

Astragaloside IV attenuates hypoxia‑induced pulmonary vascular remodeling via the Notch signaling pathway

et al. 2020

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The Notch signaling pathway participates in pulmonary artery smooth muscle cell (PASMC) proliferation and apoptosis. Astragaloside IV (AS-IV) is an effective antiproliferative treatment for vascular diseases. The present study aimed to investigate the protective effects and mechanisms underlying AS-IV on hypoxia-induced PASMC proliferation and pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) model rats. Rats were divided into the following four groups: i) normoxia; ii) hypoxia (10% O 2); iii) treatment, hypoxia + intragastrical administration of AS-IV (2 mg/kg) daily for 28 days; and iv) DAPT, hypoxia + AS-IV treatment + subcutaneous administration of DAPT (10 mg/kg) three times daily. The effects of AS-IV treatment on the development of hypoxia-induced PAH, right ventricle (RV) hypertrophy and pulmonary vascular remodeling were examined. Furthermore, PASMCs were treated with 20 µmol/l AS-IV under hypoxic conditions for 48 h. To determine the effect of Notch signaling in vascular remodeling and the potential mechanisms underlying AS-IV treatment, 5 mmol/l γ-secretase inhibitor [N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT)] was used. Cell viability and apoptosis were determined by performing the MTT assay and flow cytometry, respectively. Immunohistochemistry was conducted to detect the expression of proliferating cell nuclear antigen (PCNA). Moreover, the mRNA and protein expression levels of Notch-3, Jagged-1, hes family bHLH transcription factor 5 (Hes-5) and PCNA were measured via reverse transcription-quantitative PCR and western blotting, respectively. Compared with the normoxic group, hypoxia-induced PAH model rats displayed characteristics of PAH and RV hypertrophy, whereas AS-IV treatment alleviated PAH and prevented RV hypertrophy. AS-IV also inhibited hypoxia-induced pulmonary vascular remodeling, as indicated by reduced wall thickness and increased lumen diameter of pulmonary arterioles, and decreased muscularization of distal pulmonary vasculature in hypoxia-induced PAH model rats. Compared with normoxia, hypoxia promoted PASMC proliferation in vitro, whereas AS-IV treatment inhibited hypoxia-induced PASMC proliferation by downregulating PCNA expression in vitro and in vivo. In hypoxia-treated PAH model rats and cultured PASMCs, AS-IV treatment reduced the expression levels of Jagged-1, Notch-3 and Hes-5. Furthermore, Notch signaling inhibition via DAPT significantly inhibited the pulmonary vascular remodeling effect of AS-IV in vitro and in vivo. Collectively, the results indicated that AS-IV effectively reversed hypoxia-induced pulmonary vascular remodeling and PASMC proliferation via the Notch signaling pathway. Therefore, the present study provided novel insights into the mechanism underlying the use of AS-IV for treatment of vascular diseases, such as PAH.

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Section: Discussionsupporting

confidence: 87%

Astragaloside IV attenuates hypoxia‑induced pulmonary vascular remodeling via the Notch signaling pathway

et al. 2020

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“…Liang et al. (2020) have reported that miRNA‐210 can regulate the expression of the HIF/VEGF/Notch pathway‐associated molecules and participate in the process of promoting angiogenesis after hypoxia. In previous research, the expression of VEGF is regulated by many miRNAs, and it is predicted by computer software that miRNA‐210 can regulate VEGF, which affects the process of angiogenesis (Hua et al., 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In hypoxia, miRNA-210 promotes endothelial cells to form blood vessels by inhibiting the expression of the target gene ephrin A3 (Ivan et al, 2008). Liang et al (2020) have reported that miRNA-210 can regulate the expression of the HIF/VEGF/Notch pathway-associated molecules and participate in the process of promoting angiogenesis after hypoxia.…”

Section: Gsyrd Regulated Mirna-210 and Ephrin A3 Expressionsmentioning

confidence: 99%

Modified Renshen Yangrong decoction enhances angiogenesis in ischemic stroke through promotion of MicroRNA‐210 expression by regulating the HIF/VEGF/Notch signaling pathway

et al. 2021

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Objective: This study aims to investigate the efficacy of modified Ginseng Yangrong decoction (GSYRD) promoting angiogenesis after ischemic stroke. Methods:In an in vivo study, rats that survived surgery were allocated into four groups: the control group and model group were treated with normal saline, the GSYRD group was treated with 18.9 mg/kg of GSYRD daily, and the positive control group was treated with Tongxinluo (TXL) (1 g/kg/d). At the end of the seven-day treatment, the area of cerebral infarction, the expression changes of miRNA-210 and ephrin A3 were determined. In an in vitro study, HUVECs were divided into a normal control serum group (NC group), normal control serum OGD group (Oxygen Glucose Deprivation group) (OGD group), OGD + drug-containing serum group (OGD+GSYRD group), and OGD + drug-containing serum + ES group (Endostatin group) (OGD+GSYRD+ES group). The cells in all groups except the NC group were cultured in a sugar-free DMEM medium under hypoxia for 48 h. Cell proliferation, angiogenic structure formation ability, the expression changes of miRNA-210, ephrin A3, and the HIF/VEGF/Notch signaling pathway-related molecules were determined. Results:In vivo, GSYRD significantly reduced infarct size (p < .01), the expression of miRNA-210 and ephrin A3 were decreased in the GSYRD group (p < .05). In vitro, the cell proliferation and tube formation ability were significantly increased in the GSYRD group (p < .05), and the expression of miRNA-210 and ephrin A3 was decreased (p < .05). In addition, in the GSYRD group, the expression of the HIF/VEGF/Notch signaling pathway-related molecules was significantly increased (p < .01 or p < .05). Conclusion:GSYRD promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA-210.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…Astragaloside IV (AS-IV) is the main active component of AR. Many studies have proven that AS-IV can promote neurogenesis and angiogenesis and improve neurological function [ 24 , 25 ]. In addition, AS-IV negatively modulates endoplasmic reticulum stress-mediated apoptosis in endothelial cells to inhibit the increase in BBB permeability induced by ischemia/reperfusion and decrease the brain infarction ratio [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction

Wang

Zhang

Liu

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Huangqi Chifeng Tang (HQCFT), a traditional Chinese formula of three herbs, has been used to treat cerebral infarction (CI). Saposhnikoviae Radix (SR) was designed as a guiding drug for HQCFT to improve its angiogenic and anti-inflammatory effects. In this study, TTC staining was used to detect the area of CI. H&E staining was used to detect the histopathologic changes in the cerebral tissue. Western blotting was performed to detect the protein expression of NLRP3, caspase 1, IL-1β, IL-6, TNF-α, MMP-9, VEGF, and VEGFR2 in cerebral tissue. Immunohistochemistry was used to detect the protein expression of MMP-9, VEGF, and VEGFR2. The contents of HIF-1α, NLRP3, caspase 1, IL-1β, IL-6, and TNF-α in the serum were determined by ELISA. Our study showed that HQCFT and HQCFT-SR could improve the pathological condition and reduce the infarcted area of the brain tissue in a rat model. In addition, HQCFT and HQCFT-SR significantly decreased the expression levels and serum contents of NLRP3, caspase 1, IL-1β, IL-6, and TNF-α; increased the expression levels of the VEGF and VEGFR2 proteins; and obviously reduced the serum content of HIF-1α. Importantly, the cytokines in brain tissue and serum from the HQCFT group exhibited better efficacy than those from the HQCFT-SR group. HQCFT exerted significant angiogenic and anti-inflammatory effects in rats subjected to middle cerebral artery occlusion (MCAO); these effects can be attributed to the guiding and enhancing effect of SR.

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

Abstract: This article has been retracted, and the online PDF has been watermarked “RETRACTED”. A retraction notice is available at DOI: 10.3233/RNN-239001.

Cited by 30 publications

References 28 publications

Astragaloside IV attenuates hypoxia‑induced pulmonary vascular remodeling via the Notch signaling pathway

Astragaloside IV attenuates hypoxia‑induced pulmonary vascular remodeling via the Notch signaling pathway

Modified Renshen Yangrong decoction enhances angiogenesis in ischemic stroke through promotion of MicroRNA‐210 expression by regulating the HIF/VEGF/Notch signaling pathway

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction

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