ArticlePloS one2017
Activation of G protein-coupled estrogen receptor 1 induces coronary artery relaxation via Epac/Rap1-mediated inhibition of RhoA/Rho kinase pathway in parallel with PKA.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- Substrate stiffness regulates HIF-1α signalling via β1-integrin/myosin-2/NF-κB axis.Journal of translational medicine · 2026Article
- Acidosis Regulates Microtubule Dynamics via the β1 Integrin/RhoA/CRMP-2 Axis.Journal of the American Chemical Society · 2026Article
- Sonoepigenetic Modification Mechanoprimes Early Osteogenic Commitment in Mesenchymal Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes.Cellular & molecular biology letters · 2024Review
- A low androgen state impairs erectile function by suppressingTranslational andrology and urology · 2023Article
- The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology.Biomolecules · 2023Review
- The G protein-coupled oestrogen receptor GPER in health and disease: an update.Nature reviews. Endocrinology · 2023Review
- A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility.Cell · 2022Article
- G-Protein-Coupled Estrogen Receptor Expression in Rat Uterine Artery Is Increased by Pregnancy and Induces Dilation in a CaInternational journal of molecular sciences · 2022Article
- Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism.Journal of oncology · 2022Article
- Histone deacetylase 8 interacts with the GTPase SmRho1 in Schistosoma mansoni.PLoS neglected tropical diseases · 2021Article
- Vascular Stiffening Mediated by Rho-Associated Coiled-Coil Containing Kinase Isoforms.Journal of the American Heart Association · 2021Article
- Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering.International journal of molecular sciences · 2021Article
- Article
- Signalling mechanisms in the cardiovascular protective effects of estrogen: With a focus on rapid/membrane signalling.Current research in physiology · 2021Review
- Sex Differences in the Vasodilation Mediated by G Protein-Coupled Estrogen Receptor (GPER) in Hypertensive Rats.Frontiers in physiology · 2021Article
- Regulation of smooth muscle contraction by monomeric non-RhoA GTPases.British journal of pharmacology · 2020Review
- Integration of Rap1 and Calcium Signaling.International journal of molecular sciences · 2020Review
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previously, we reported that cAMP/PKA signaling is involved in GPER-mediated coronary relaxation by activating MLCP via inhibition of RhoA pathway. In the current study, we tested the hypothesis that activation of GPER induces coronary artery relaxation via inhibition of RhoA/Rho kinase pathway by cAMP downstream targets, exchange proteins directly activated by cAMP (Epac) as well as PKA. Our results show that Epac inhibitors, brefeldin A (BFA, 50 μM), or ESI-09 (20 μM), or CE3F4 (100 μM), all partially inhibited porcine coronary artery relaxation response to the selective GPER agonist, G-1 (0.3-3 μM); while concurrent administration of BFA and PKI (5 μM), a PKA inhibitor, almost completely blocked the relaxation effect of G-1. The Epac specific agonist, 8-CPT-2Me-cAMP (007, 1-100 μM), induced a concentration-dependent relaxation response. Furthermore, the activity of Ras-related protein 1 (Rap1) was up regulated by G-1 (1 μM) treatment of porcine coronary artery smooth muscle cells (CASMCs). Phosphorylation of vasodilator-stimulated phosphoprotein (p-VASP) was elevated by G-1 (1 μM) treatment, but not by 007 (50 μM); and the effect of G-1 on p-VASP was blocked by PKI, but not by ESI-09, an Epac antagonist. RhoA activity was similarly down regulated by G-1 and 007, whereas ESI-09 restored most of the reduced RhoA activity by G-1 treatment. Furthermore, G-1 decreased PGF2α-induced p-MYPT1, which was partially reversed with either ESI-09 or PKI; whereas, concurrent administration of ESI-09 and PKI totally prevented the inhibitory effect of G-1. The inhibitory effects of G-1 on p- MLC levels in CASMCs were mostly restored by either ESI-09 or PKI. These results demonstrate that activation of GPER induces coronary artery relaxation via concurrent inhibition of RhoA/Rho kinase by Epac/Rap1 and PKA. GPER could be a potential drug target for preventing and treating cardiovascular diseases.
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