2. Academic Validation
  3. Isoimperatorin Inhibits Angiogenesis by Suppressing VEGFR2 Signaling Pathway

Isoimperatorin Inhibits Angiogenesis by Suppressing VEGFR2 Signaling Pathway

  • Cardiovasc Drugs Ther. 2024 Feb 16. doi: 10.1007/s10557-024-07561-5.
Yating Xu 1 2,  Di Xia 1 3 4,  Shan Deng 5 6 7 8,  Minglu Liang 9 10 11
Affiliations

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.
  • 2 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Cardiovascular Center, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan, 430022, China. [email protected].
  • 6 Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 7 Hubei clinical research center for metabolic and cardiovascular disease, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 8 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 9 Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan, 430022, China. [email protected].
  • 10 Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 11 Hubei clinical research center for metabolic and cardiovascular disease, Huazhong University of Science and Technology, Wuhan, China. [email protected].
PMID: 38363479 DOI: 10.1007/s10557-024-07561-5
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/KDR/Flk-1 and its downstream signaling pathways activation.

Conclusions: Our study showed that isoimperatorin suppressed angiogenesis by targeting the VEGFR2/KDR/Flk-1 signaling pathway and could be a potential therapeutic agent for targeting angiogenesis.

Keywords

Angiogenesis; Isoimperatorin; VEGF; VEGFR2.

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