ArticleJournal of molecular and cellular cardiology2011
PKA and Epac synergistically inhibit smooth muscle cell proliferation.
Article in Journal of molecular and cellular cardiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
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- Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.Nature metabolism · 2024Article
- Energy Regulation in Inflammatory Sarcopenia by the Purinergic System.International journal of molecular sciences · 2023Review
- Protease-Activated Receptor 2 Controls Vascular Smooth Muscle Cell Proliferation in Cyclic AMP-Dependent Protein Kinase/Mitogen-Activated Protein Kinase Kinase 1/2-Dependent Manner.Journal of vascular research · 2023Article
- Quantifying and mathematical modelling of the influence of soluble adenylate cyclase on cell cycle in human endothelial cells with Bayesian inference.Journal of cellular and molecular medicine · 2022Article
- Role of PDE10A in vascular smooth muscle cell hyperplasia and pathological vascular remodelling.Cardiovascular research · 2022Article
- Epac2 in midbrain dopamine neurons contributes to cocaine reinforcement via enhancement of dopamine release.eLife · 2022Article
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- GPCR-mediated YAP/TAZ inactivation in fibroblasts via EPAC1/2, RAP2C, and MAP4K7.Journal of cellular physiology · 2021Article
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- Epigenetic Regulation of Pulmonary Arterial Hypertension-Induced Vascular and Right Ventricular Remodeling: New Opportunities?International journal of molecular sciences · 2020Review
- The Role of Epac in Cancer Progression.International journal of molecular sciences · 2020Review
- EPAC in Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020Review
- Nuclear actin regulates cell proliferation and migration via inhibition of SRF and TEAD.Biochimica et biophysica acta. Molecular cell research · 2020Article
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- Review
- Neuropeptide Y release in the rat spinal cord measured with Y1 receptor internalization is increased after nerve injury.Neuropharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Cyclic AMP signalling promotes VSMC quiescence in healthy vessels and during vascular healing following injury. Cyclic AMP inhibits VSMC proliferation via mechanisms that are not fully understood. We investigated the role of PKA and Epac signalling on cAMP-induced inhibition of VSMC proliferation. cAMP-mediated growth arrest was PKA-dependent. However, selective PKA activation with 6-Benzoyl-cAMP did not inhibit VSMC proliferation, indicating a requirement for additional pathways. Epac activation using the selective cAMP analogue 8-CPT-2'-O-Me-cAMP, did not affect levels of hyperphosphorylated Retinoblastoma (Rb) protein, a marker of G1-S phase transition, or BrdU incorporation, despite activation of the Epac-effector Rap1. However, 6-Benzoyl-cAMP and 8-CPT-2'-O-Me-cAMP acted synergistically to inhibit Rb-hyperphosphorylation and BrdU incorporation, indicating that both pathways are required for growth inhibition. Consistent with this, constitutively active Epac increased Rap1 activity and synergised with 6-Benzoyl-cAMP to inhibit VSMC proliferation. PKA and Epac synergised to inhibit phosphorylation of ERK and JNK. Induction of stellate morphology, previously associated with cAMP-mediated growth arrest, was also dependent on activation of both PKA and Epac. Rap1 inhibition with Rap1GAP or siRNA silencing did not negate forskolin-induced inhibition of Rb-hyperphosphorylation, BrdU incorporation or stellate morphology. This data demonstrates for the first time that Epac synergises with PKA via a Rap1-independent mechanism to mediate cAMP-induced growth arrest in VSMC. This work highlights the role of Epac as a major player in cAMP-dependent growth arrest in VSMC.
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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.