ArticleArteriosclerosis, thrombosis, and vascular biology2015
Novel role of reactive oxygen species-activated Trp melastatin channel-2 in mediating angiogenesis and postischemic neovascularization.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- The role of TRPV4 in ischemic stroke.Molecular brain · 2026Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- TRPM2: a pivotal player in tumor progression and a promising therapeutic target.Cancer cell international · 2025Review
- Effect of topical ramucirumab in experimental corneal neovascularization model.International ophthalmology · 2025Article
- The role of transient receptor potential channels in chronic kidney disease-mineral and bone disorder.Frontiers in pharmacology · 2025Review
- A TRP to Pathological Angiogenesis and Vascular Normalization.Comprehensive Physiology · 2024Review
- Activation of endothelial TRPM2 exacerbates blood-brain barrier degradation in ischemic stroke.Cardiovascular research · 2024Article
- Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives.Journal of translational medicine · 2023Review
- Simultaneous Inhibition of Thrombosis and Inflammation Is Beneficial in Treating Acute Myocardial Infarction.International journal of molecular sciences · 2023Article
- Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM7.Frontiers in cell and developmental biology · 2023Review
- Transient Receptor Potential (TRP) Channels in Tumor Vascularization.International journal of molecular sciences · 2022Review
- Calcium-Permeable Channels in Tumor Vascularization: Peculiar Sensors of Microenvironmental Chemical and Physical Cues.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Reactive Oxygen Species and Endothelial CaInternational journal of molecular sciences · 2021Review
- The Role of TRPM2 in Endothelial Function and Dysfunction.International journal of molecular sciences · 2021Review
- Bevacizumab induces oxidative cytotoxicity and apoptosis via TRPM2 channel activation in retinal pigment epithelial cells: Protective role of glutathione.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2021Article
- Reactive Oxygen Species-Induced TRPM2-Mediated CaAntioxidants (Basel, Switzerland) · 2021Review
- Review
- Endothelial response boosted by platelet lysate: the involvement of calcium toolkit.International journal of molecular sciences · 2020Article
- Towards Novel Geneless Approaches for Therapeutic Angiogenesis.Frontiers in physiology · 2020Article
- Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel.eLife · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTransient receptor potential melastatin-2 (TRPM2) channel is a nonselective cation channel that mediates influx of Ca(2+) and Na(+) with relative permeability of PCa:PNa ≈0.6 in response to cellular oxidative stress. As angiogenesis and ischemic neovascularization are both significantly dependent on oxidant signaling, here we investigated the possible role of vascular endothelial growth factor (VEGF)-induced reactive oxygen species production in activating TRPM2-dependent Ca(2+) signaling and in the mechanism of angiogenesis and ischemic neovascularization. APPROACH AND
resultsWe observed that VEGF stimulation rapidly induced the association of TRPM2 and cellular Src kinase with vascular endothelial-cadherin forming a signalplex at vascular endothelial-cadherin junctions in endothelial cells. Using endothelial cells isolated from TRPM2(-/-) mice or after small interfering RNA depletion of TRPM2, we demonstrated that TRPM2-activated Ca(2+) signaling was required for cellular Src kinase-induced phosphorylation of vascular endothelial-cadherin at Y658 and Y731, the crucial sites involved in vascular endothelial-cadherin internalization in response to VEGF. VEGF-induced reactive oxygen species generation activated TRPM2-induced Ca(2+) entry, whereas the reactive oxygen species-insensitive TRPM2 mutant (C1008→A) showed impaired Ca(2+) entry. Endothelial cells depleted of TRPM2 also displayed significantly perturbed migratory phenotype and impaired activation of cellular Src in response to VEGF. TRPM2(-/-) mice reconstituted with wild-type myeloid cells demonstrated aberrant angiogenesis and neovascularization in the hindlimb ischemia model as compared with wild-type mice.
conclusionsVEGF-induced angiogenesis and postischemic neovascularization in mice required reactive oxygen species generation in endothelial cells and resultant TRPM2 activation. Thus, our findings provide novel insight into the role of TRPM2 in mechanism of angiogenesis and ischemic neovascularization.
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