ArticleScience advances2020
Epac1 inhibition ameliorates pathological angiogenesis through coordinated activation of Notch and suppression of VEGF signaling.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Endothelial Epac1 facilitates YAP/TAZ controlled melanoma growth and angiogenesis.Angiogenesis · 2026Article
- Epac1 deletion attenuates Müller glial pathological activation and mitigates retinal neurodegeneration in ischemia-induced retinopathy.Journal of advanced research · 2026Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Cyclic nucleotide signaling as a drug target in retinitis pigmentosa.FEBS letters · 2025Review
- In situ vascularization and epithelialization of segmental bioengineered trachea based on marrow-derived stem/progenitor cells.Materials today. Bio · 2025Article
- Reduced blood EPAC1 protein levels as a marker of severe coronary artery disease: the role of hypoxic foam cell-transformed smooth muscle cells.Journal of translational medicine · 2025Article
- A SUMO-interacting motif in the guanine nucleotide exchange factor EPAC1 is required for subcellular targeting and function.bioRxiv : the preprint server for biology · 2025Article
- Metabolism in the tumor microenvironment: implications for pathogenesis and therapeutics.Frontiers in immunology · 2025Review
- Decreased CREB phosphorylation impairs embryonic retinal neurogenesis in thebioRxiv : the preprint server for biology · 2024Article
- FAM222A, Part of the BET-Regulated Basal Endothelial Transcriptome, Is a Novel Determinant of Endothelial Biology and Angiogenesis-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- PERK Inhibition Suppresses Neovascularization and Protects Neurons During Ischemia-Induced Retinopathy.Investigative ophthalmology & visual science · 2023Article
- Upregulation of Epac1 Promotes Pericyte Loss by Inducing Mitochondrial Fission, Reactive Oxygen Species Production, and Apoptosis.Investigative ophthalmology & visual science · 2023Article
- Membranes prime the RapGEF EPAC1 to transduce cAMP signaling.Nature communications · 2023Article
- Angiotensin-converting enzyme inhibitor promotes angiogenesis through Sp1/Sp3-mediated inhibition of notch signaling in male mice.Nature communications · 2023Article
- The peripheral Epac1/p-Cav-1 pathway underlies the disruption of the vascular endothelial barrier following skin/muscle incision and retraction-induced chronic postsurgical pain.Annals of translational medicine · 2022Article
- Suppression of Pathological Ocular Neovascularization by a Small Molecular Multi-Targeting Kinase Inhibitor, DCZ19903.Translational vision science & technology · 2022Article
- Angiogenic stem cell delivery platform to augment post-infarction neovasculature and reverse ventricular remodeling.Scientific reports · 2022Article
- Epac1 activation by cAMP regulates cellular SUMOylation and promotes the formation of biomolecular condensates.Science advances · 2022Article
- Epac1-/- and Epac2-/- mice exhibit deficient epithelial Na+ channel regulation and impaired urinary Na+ conservation.JCI insight · 2022Article
- Secretogranin III stringently regulates pathological but not physiological angiogenesis in oxygen-induced retinopathy.Cellular and molecular life sciences : CMLS · 2022Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
In this study, we investigated the roles of Epac1 in pathological angiogenesis and its potential as a novel therapeutic target for the treatment of vasoproliferative diseases. Genetic deletion of Epac1 ameliorated pathological angiogenesis in mouse models of oxygen-induced retinopathy (OIR) and carotid artery ligation. Moreover, genetic deletion or pharmacological inhibition of Epac1 suppressed microvessel sprouting from ex vivo aortic ring explants. Mechanistic studies revealed that Epac1 acted as a previously unidentified inhibitor of the γ-secretase/Notch signaling pathway via interacting with γ-secretase and regulating its intracellular trafficking while enhancing vascular endothelial growth factor signaling to promote pathological angiogenesis. Pharmacological administration of an Epac-specific inhibitor suppressed OIR-induced neovascularization in wild-type mice, recapitulating the phenotype of genetic Epac1 knockout. Our results demonstrate that Epac1 signaling is critical for the progression of pathological angiogenesis but not for physiological angiogenesis and that the newly developed Epac-specific inhibitors are effective in combating proliferative retinopathy.
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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.