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Isoimperatorin Inhibits Angiogenesis by Suppressing VEGFR2 Signaling Pathway

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Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Purpose

Angiogenesis involves in many pathological processes, including tumor metastasis, diabetic retinopathy, and rheumatoid arthritis. Therefore, identifying therapeutic drugs that target angiogenesis may be a promising strategy for disease treatment. Isoimperatorin is a furanocoumarin with anti-inflammatory and anti-microbial effects. However, the impacts of isoimperatorin on angiogenesis and its underlying mechanisms remain unclear. This study aimed to verify its effects on vascular endothelial growth factor (VEGF)-induced endothelial angiogenesis.

Methods

We employed various assays including 5-ethynyl-2′-deoxyuridine incorporation assay, transwell migration assay, wound healing assay, tube formation assay, and Western blot to evaluate the effects of isoimperatorin on angiogenesis in vitro. Additionally, we utilized Western blot and immunofluorescence analysis to examine the activation of vascular endothelial growth factor receptor (VEGFR) 2 and its downstream signaling pathways following isoimperatorin treatment. To further validate the anti-angiogenic effects of isoimperatorin in vivo, we conducted a matrigel plug assay and established an orthotopic tumor model.

Results

We demonstrated that pretreatment with isoimperatorin inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation. Isoimperatorin also suppressed angiogenesis in vivo in a matrigel plug assay and in an orthotopic tumor model. Our results revealed that isoimperatorin exhibited anti-angiogenic effects via inhibiting VEGFR2 and its downstream signaling pathways activation.

Conclusions

Our study showed that isoimperatorin suppressed angiogenesis by targeting the VEGFR2 signaling pathway and could be a potential therapeutic agent for targeting angiogenesis.

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Data Availability

The data are available from the corresponding author upon reasonable request. The unprocessed Western blot images were in the supplementary data.

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Funding

This study was supported by the Natural Science Foundation of Hubei Province (2020CFB429).

Author information

Authors and Affiliations

  1. Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan, 430022, China

    Yating Xu, Di Xia, Shan Deng & Minglu Liang

  2. Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, China

    Di Xia, Shan Deng & Minglu Liang

  3. Hubei clinical research center for metabolic and cardiovascular disease, Huazhong University of Science and Technology, Wuhan, China

    Shan Deng & Minglu Liang

  4. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Yating Xu & Shan Deng

  5. Cardiovascular Center, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Di Xia

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  1. Yating Xu
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Contributions

YTX: conducting the experiments, manuscript writing. DX: data analysis. SD: Supervision, study design, manuscript revision. MLL: Supervision, manuscript revision.

Corresponding authors

Correspondence to Shan Deng or Minglu Liang.

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Ethics Approval

Approval for all animal experimental procedures was obtained from the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (permit number: [2023] IACUC Number 3393). All animal experimental procedures were conducted in strict adherence to applicable institutional and national regulations and guidelines.

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Not applicable.

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The authors declare no conflicts of interest.

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Xu, Y., Xia, D., Deng, S. et al. Isoimperatorin Inhibits Angiogenesis by Suppressing VEGFR2 Signaling Pathway. Cardiovasc Drugs Ther (2024). https://doi.org/10.1007/s10557-024-07561-5

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  • DOI: https://doi.org/10.1007/s10557-024-07561-5

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