ArticleThe Journal of biological chemistry2011
Angiogenic functions of voltage-gated Na+ Channels in human endothelial cells: modulation of vascular endothelial growth factor (VEGF) signaling.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 103 citations in OpenAlex.
- Voltage-Dependent Ion Channels in Vascular Endothelial Cells: An Unexpected Signaling Pathway in Non-Excitable Cells.Biomedicines · 2026Review
- Functional Coupling Between Voltage-Dependent Sodium Channels and Activation of the CaInternational journal of molecular sciences · 2026Article
- Intersection Between Local Anesthetics and Cancer Biology: What Now? Where Are We Going?Advanced biology · 2025Review
- A Novel Function of NaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Sodium channels in non-excitable cells: powerful actions and therapeutic targets beyond Hodgkin and Huxley.Trends in cell biology · 2025Review
- Single-Cell Transcriptomic Analysis of Kaposi Sarcoma.PLoS pathogens · 2025Article
- The ion transport, GPCR, and RTK toolkit expression in the human cerebrovascular endothelial cell line, hCMEC/D3: an Omics perspective.Frontiers in physiology · 2025Article
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- Nanotechnology and Cancer Bioelectricity: Bridging the Gap Between Biology and Translational Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Store-Operated CaJournal of clinical medicine · 2023Review
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- NCX2 Regulates Intracellular Calcium Homeostasis and Translocation of HIF-1α into the Nucleus to Inhibit Glioma Invasion.Biochemical genetics · 2023Article
- Tetrodotoxin Decreases the Contractility of Mesenteric Arteries, Revealing the Contribution of Voltage-Gated NaMarine drugs · 2023Article
- Voltage-gated sodium channels: from roles and mechanisms in the metastatic cell behavior to clinical potential as therapeutic targets.Frontiers in pharmacology · 2023Review
- Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives.Biomolecules · 2022Review
- Neonatal Nav1.5 Protein Expression in Human Colorectal Cancer: Immunohistochemical Characterization and Clinical Evaluation.Cancers · 2021Article
- VEGF as a potential molecular target in periodontitis: a meta-analysis and microarray data validation.Journal of inflammation (London, England) · 2021Article
- A protocol for simultaneous CaSTAR protocols · 2021Article
- Breast cancer therapy affects the expression of antineonatal Nav1.5 antibodies in the serum of patients with breast cancer.Oncology letters · 2021Article
- Fibroblast Growth Factor-1 Activates Neurons in the Arcuate Nucleus and Dorsal Vagal Complex.Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Voltage-gated sodium channel (VGSC) activity has previously been reported in endothelial cells (ECs). However, the exact isoforms of VGSCs present, their mode(s) of action, and potential role(s) in angiogenesis have not been investigated. The main aims of this study were to determine the role of VGSC activity in angiogenic functions and to elucidate the potentially associated signaling mechanisms using human umbilical vein endothelial cells (HUVECs) as a model system. Real-time PCR showed that the primary functional VGSC α- and β-subunit isoforms in HUVECs were Nav1.5, Nav1.7, VGSCβ1, and VGSCβ3. Western blots verified that VGSCα proteins were expressed in HUVECs, and immunohistochemistry revealed VGSCα expression in mouse aortic ECs in vivo. Electrophysiological recordings showed that the channels were functional and suppressed by tetrodotoxin (TTX). VGSC activity modulated the following angiogenic properties of HUVECs: VEGF-induced proliferation or chemotaxis, tubular differentiation, and substrate adhesion. Interestingly, different aspects of angiogenesis were controlled by the different VGSC isoforms based on TTX sensitivity and effects of siRNA-mediated gene silencing. Additionally, we show for the first time that TTX-resistant (TTX-R) VGSCs (Nav1.5) potentiate VEGF-induced ERK1/2 activation through the PKCα-B-RAF signaling axis. We postulate that this potentiation occurs through modulation of VEGF-induced HUVEC depolarization and [Ca(2+)](i). We conclude that VGSCs regulate multiple angiogenic functions and VEGF signaling in HUVECs. Our results imply that targeting VGSC expression/activity could be a novel strategy for controlling angiogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.