ArticlePhysiological reports2014
cAMP controls the restoration of endothelial barrier function after thrombin-induced hyperpermeability via Rac1 activation.
Article in Physiological reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Active Endothelial Inactivation of Hyperpermeability: The Role of Nitric Oxide-Driven cAMP/Epac1 Signaling.Journal of cardiovascular development and disease · 2025Review
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Review
- Cortactin is in a complex with VE-cadherin and is required for endothelial adherens junction stability through Rap1/Rac1 activation.Scientific reports · 2024Article
- Off-Target Effects of P2Y12 Receptor Inhibitors: Focus on Early Myocardial Fibrosis Modulation.International journal of molecular sciences · 2023Review
- CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- ZNF185 prevents stress fiber formation through the inhibition of RhoA in endothelial cells.Communications biology · 2023Article
- Feedback between mechanosensitive signaling and active forces governs endothelial junction integrity.Nature communications · 2022Article
- Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro.International journal of molecular sciences · 2022Article
- Review
- Protease-activated receptor 2 promotes clearance ofFrontiers in pharmacology · 2022Article
- The Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner.Biomolecules · 2021Article
- Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2021Review
- Purinergic Regulation of Endothelial Barrier Function.International journal of molecular sciences · 2021Review
- The Potentially Therapeutic Role of EPAC in Curbing the Process of Idiopathic Pulmonary Fibrosis via Differential Cellular Pathways.Journal of inflammation research · 2021Article
- Cx43 and the Actin Cytoskeleton: Novel Roles and Implications for Cell-Cell Junction-Based Barrier Function Regulation.Biomolecules · 2020Review
- Evaluation of active Rac1 levels in cancer cells: A case of misleading conclusions from immunofluorescence analysis.The Journal of biological chemistry · 2020Article
- Extracellular adenosine enhances pulmonary artery vasa vasorum endothelial cell barrier function via Gi/ELMO1/Rac1/PKA-dependent signaling mechanisms.American journal of physiology. Cell physiology · 2020Article
- Inhibition of Protein Prenylation of GTPases Alters Endothelial Barrier Function.International journal of molecular sciences · 2019Article
- Activation of Notch signaling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway.American journal of physiology. Heart and circulatory physiology · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammatory mediators like thrombin disrupt endothelial adherens junctions (AJs) and barrier integrity leading to oedema formation followed by resealing of AJs and a slow recovery of the barrier function. The molecular mechanisms of this process have not yet been fully delineated. The aim of the present study was to analyse the molecular mechanism of endothelial barrier recovery and thrombin was used as model inflammatory mediator. Thrombin caused a strong increase in endothelial permeability within 10 min accompanied by loss of Rac1 but not cdc42 activity, drop in cellular cAMP contents, and a strong activation of the endothelial contractile machinery mainly via RhoA/Rock signalling. Activation of RhoA/Rock signalling precedes and is dependent upon a rise in the cytosolic Ca(2+) concentration. Inhibition of cytosolic Ca(2+) rise but not MLCK or Rock enhances the recovery of endothelial barrier function. The cellular cAMP contents increased gradually during the barrier recovery phase (30-60 min after thrombin challenge) accompanied by an increase in Rac1 activity. Inhibition of Rac1 activity using a specific pharmacological inhibitor (NSC23766) abrogated the endothelial barrier recovery process, suggesting a Rac1-dependent phenomenon. Likewise, inhibition of either adenylyl cyclase or the cAMP-effectors PKA and Epac (with PKI and ESI-09, respectively) caused an abrogation of Rac1 activation, resealing of endothelial AJs and recovery of endothelial barrier function. The data demonstrate that endothelial barrier recovery after thrombin challenge is regulated by Rac1 GTPase activation. This Rac1 activation is due to increased levels of cellular cAMP and activation of downstream signalling during the barrier recovery phase.
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