ArticleThe Journal of investigative dermatology2015
Activation of the Thromboxane A2 Receptor by 8-Isoprostane Inhibits the Pro-Angiogenic Effect of Vascular Endothelial Growth Factor in Scleroderma.
Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Insights into the Expression, Structure, and Function of the Thromboxane AACS pharmacology & translational science · 2025Review
- RhoA/rho kinase pathway activation in age-associated endothelial cell dysfunction and thrombosis.Journal of cellular and molecular medicine · 2024Review
- Inhibition of TP signaling promotes endometriosis growth and neovascularization.Molecular medicine reports · 2023Article
- Single-cell RNA-seq and bulk-seq identify RAB17 as a potential regulator of angiogenesis by human dermal microvascular endothelial cells in diabetic foot ulcers.Burns & trauma · 2023Article
- A Thromboxane AArteriosclerosis, thrombosis, and vascular biology · 2022Article
- Rho GTPase signaling in rheumatic diseases.iScience · 2022Review
- Upcoming treatments for morphea.Immunity, inflammation and disease · 2021Review
- Epigenetic down-regulation of microRNA-126 in scleroderma endothelial cells is associated with impaired responses to VEGF and defective angiogenesis.Journal of cellular and molecular medicine · 2021Article
- Dissecting the Cellular Mechanism of Prostacyclin Analog Iloprost in Reversing Vascular Dysfunction in Scleroderma.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Lipid Alterations in Systemic Sclerosis.Frontiers in molecular biosciences · 2021Review
- Lipid Metabolism Profiles in Rheumatic Diseases.Frontiers in pharmacology · 2021Review
- Identification of Cysteine-Rich Angiogenic Inducer 61 as a Potential Antifibrotic and Proangiogenic Mediator in Scleroderma.Arthritis & rheumatology (Hoboken, N.J.) · 2019Article
- Sex, Oxidative Stress, and Hypertension: Insights From Animal Models.Physiology (Bethesda, Md.) · 2019Review
- In Systemic Sclerosis, a Unique Long Non Coding RNA Regulates Genes and Pathways Involved in the Three Main Features of the Disease (Vasculopathy, Fibrosis and Autoimmunity) and in Carcinogenesis.Journal of clinical medicine · 2019Article
- Inhibition of EZH2 prevents fibrosis and restores normal angiogenesis in scleroderma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Histone Deacetylase 5 Is Overexpressed in Scleroderma Endothelial Cells and Impairs Angiogenesis via Repression of Proangiogenic Factors.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The pathogenesis of scleroderma (SSc) includes components of autoimmunity, vascular dysfunction, and accumulation of extracellular matrix. 8-isoprostane, an oxidized lipid created by oxidative stress, activates the thromboxane A2 receptor (TXAR) and the Rho-associated kinase (ROCK) pathway. In this study, we determined whether the TXAR was activated by 8-isoprostane in SSc endothelial cells (ECs) and whether this pathway inhibited VEGF-induced angiogenesis. Elevated 8-isoprostane was observed in plasma and conditioned media from SSc patients. SSc-conditioned media inhibited EC tube formation, whereas addition of vitamin E, by reducing 8-isoprostane, increased tube formation. VEGF did not induce angiogenesis in SSc ECs, but vitamin E or TXAR inhibition restored its effect. The expression of TXAR, RhoA, and ROCK1/2 was elevated in SSc ECs. ROCK activity and 8-isoprostane-induced ROCK activation were significantly higher in SSc ECs, whereas VEGF had no effect. The hyper-activation of the TXAR leads to inhibition of VEGF-induced angiogenesis, as inhibition of the TXAR pathway results in a blockade of 8-isoprostane-induced ROCK activation and restoration of VEGF activity. These results suggest that the TXAR pathway has a crucial role in angiogenesis and that 8-isoprostane is not just a by-product of oxidative stress but also has a significant role in the impaired angiogenesis that characterizes SSc.
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Registered trials
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