ArticleMolecular endocrinology (Baltimore, Md.)2015
Role of Nongenomic Signaling Pathways Activated by Aldosterone During Cardiac Reperfusion Injury.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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Who cites it
26 citing papers in PubMed, 66 citations in OpenAlex.
- Review
- Aldosterone: From Essential Tubular Regulator to Pathological Driver-Physiology, Disease, and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Article
- Obesity, aldosterone excess, and mineralocorticoid receptor activation: Parallel or intersected circumstances?Journal of clinical hypertension (Greenwich, Conn.) · 2024Review
- Control of sodium appetite by hindbrain aldosterone-sensitive neurons.Molecular and cellular endocrinology · 2024Review
- Interplay between caveolin-1 and mineralocorticoid receptor in cardiometabolic disease.The Journal of endocrinology · 2024Review
- Safety and efficacy of once-daily dexfadrostat phosphate in patients with primary aldosteronism: a randomised, parallel group, multicentre, phase 2 trial.EClinicalMedicine · 2024Article
- Higher plasma aldosterone concentrations in patients with aortic diseases and hypertension: a retrospective observational study.European journal of medical research · 2023Observational
- The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology.Biomolecules · 2023Review
- Aldosterone: Essential for Life but Damaging to the Vascular Endothelium.Biomolecules · 2023Review
- Cardiovascular Disease in Obstructive Sleep Apnea: Putative Contributions of Mineralocorticoid Receptors.International journal of molecular sciences · 2023Review
- G protein-coupled estrogen receptor: a promising therapeutic target for aldosterone-induced hypertension.Frontiers in endocrinology · 2023Review
- Correlation of functional and radioligand binding characteristics of GPER ligands confirming aldosterone as a GPER agonist.Pharmacology research & perspectives · 2022Article
- GRK5 is an essential co-repressor of the cardiac mineralocorticoid receptor and is selectively induced by finerenone.World journal of cardiology · 2022Article
- Integrated analysis of label-free quantitative proteomics and bioinformatics reveal insights into signaling pathways in male breast cancer.Genetics and molecular biology · 2021Article
- Mineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters.Heart and vessels · 2020Article
- Antagonistic Roles of GRK2 and GRK5 in Cardiac Aldosterone Signaling Reveal GRK5-Mediated Cardioprotection via Mineralocorticoid Receptor Inhibition.International journal of molecular sciences · 2020Article
- Zi Shen Huo Luo Formula Prevents Aldosterone-Induced Cardiomyocyte Hypertrophy and Cardiac Fibroblast Proliferation by Regulating the Striatin-Mediated MR/EGFR/ERK Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Rapid Aldosterone-Mediated Signaling in the DCT Increases Activity of the Thiazide-Sensitive NaCl Cotransporter.Journal of the American Society of Nephrology : JASN · 2019Article
- Novel Insights into the Crosstalk between Mineralocorticoid Receptor and G Protein-Coupled Receptors in Heart Adverse Remodeling and Disease.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Aldosterone (Aldo) activates both genomic and nongenomic signaling pathways in the cardiovascular system. Activation of genomic signaling pathways contributes to the adverse cardiac actions of Aldo during reperfusion injury; however, the extent nongenomic signaling pathways contribute has been difficult to identify due to lack of a specific ligand that activates only nongenomic signaling pathways. Using a pegylated aldosterone analog, aldosterone-3-carboxymethoxylamine-TFP ester conjugated to methoxypegylated amine (Aldo-PEG), we are able for the first time to distinguish between nongenomic and genomic cardiac actions of Aldo. We confirm Aldo-PEG activates phosphorylation of ERK1/2 in rat cardiomyocyte H9c2 cells similar to Aldo and G protein-coupled receptor 30 (GPR30 or GPER) agonist G1. GPER antagonist, G36, but not mineralocorticoid receptor (MR) antagonist spironolactone, prevented ERK1/2 phosphorylation by Aldo, Aldo-PEG, and G1. The selective nongenomic actions of Aldo-PEG are confirmed, with Aldo-PEG increasing superoxide production in H9c2 cells to similar levels as Aldo but having no effect on subcellular localization of MR. Striatin serves as a scaffold for GPER and MR, with GPER antagonist G36, but not spironolactone, restoring MR-striatin complexes. Aldo-PEG had no effect on MR-dependent transcriptional activation, whereas Aldo increased transcript levels of serum-regulated kinase 1 and plasminogen activator inhibitor-1. Using our ex vivo experimental rat model of myocardial infarction, we found aggravated infarct size and apoptosis by Aldo but not Aldo-PEG. Our studies confirm that in the heart, activation of nongenomic signaling pathways alone are not sufficient to trigger the deleterious effects of aldosterone during myocardial reperfusion injury.
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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.