ArticleCardiovascular research2015
The cAMP-producing agonist beraprost inhibits human vascular smooth muscle cell migration via exchange protein directly activated by cAMP.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Ultrasonography evaluation on the protective effect of combination therapy of beraprost sodium and aspirin on arteries occlusion and stiffness in patients with type 2 diabetes mellitus - a prospective, randomized study.BMC endocrine disorders · 2022Trial
- High PGEScientifica · 2026Article
- The liver talks back: NPY orchestrates attraction of cancer cells and CHK2-dependent clonogenicity in the metastatic niche.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.Nature metabolism · 2024Article
- PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets.International journal of molecular sciences · 2023Review
- Beyond epithelial damage: vascular and endothelial contributions to idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2023Review
- Article
- Expert consensus on the establishment and maintenance of native arteriovenous fistula.Chronic diseases and translational medicine · 2021Article
- Beraprost ameliorates postmenopausal osteoporosis by regulating Nedd4-induced Runx2 ubiquitination.Cell death & disease · 2021Article
- Prostaglandin I2 signaling licenses Treg suppressive function and prevents pathogenic reprogramming.The Journal of clinical investigation · 2021Article
- EPAC in Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020Review
- Activation of Inward Rectifier KBioMed research international · 2020Article
- Article
- Review
- G Protein-Coupled Estrogen Receptor Protects From Angiotensin II-Induced Increases in Pulse Pressure and Oxidative Stress.Frontiers in endocrinology · 2019Article
- Synergistic effect of phosphodiesterase 4 inhibitor and serum on migration of endotoxin-stimulated macrophages.Innate immunity · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Dual Role of CREB in The Regulation of VSMC Proliferation: Mode of Activation Determines Pro- or Anti-Mitogenic Function.Scientific reports · 2018Article
- A current view of G protein-coupled receptor - mediated signaling in pulmonary hypertension: finding opportunities for therapeutic intervention.Vessel plus · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
aimsDuring restenosis, vascular smooth muscle cells (VSMCs) migrate from the vascular media to the developing neointima. Preventing VSMC migration is therefore a therapeutic target for restenosis. Drugs, such as prostacyclin analogues, that increase the intracellular concentration of cyclic adenosine monophosphate (cAMP) can inhibit VSMC migration, but the mechanisms via which this occurs are unknown. Two main downstream mediators of cAMP are protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). This study has examined the effects of the prostacyclin analogue beraprost on VSMC migration and investigated the intracellular pathways involved. METHODS AND
resultsIn a chemotaxis chamber, human saphenous vein VSMC migrated towards a platelet-derived growth-factor-BB (PDGF) chemogradient. Incubation with therapeutically relevant concentrations of cAMP-producing agonist beraprost significantly decreased PDGF-induced migration. Direct activation of either PKA or Epac inhibited migration whereas inhibition of PKA did not prevent the anti-migratory effect of beraprost. Direct activation of Epac also prevented hyperplasia in ex vivo serum-treated human veins. Using fluorescence resonance energy transfer, we demonstrated that beraprost activated Epac but not PKA. The mechanisms of this Epac-mediated effect involved activation of Rap1 with subsequent inhibition of RhoA. Cytoskeletal rearrangement at the leading edge of the cell was consequently inhibited. Interestingly, Epac1 was localized to the leading edge of migrating VSMC.
conclusionsThese results indicate that therapeutically relevant concentrations of beraprost can inhibit VSMC migration via a previously unknown mechanism involving the cAMP mediator Epac. This may provide a novel target that could blunt neointimal formation.
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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.