ArticleCardiovascular research2015
Cardiac myosin light chain phosphorylation and inotropic effects of a biased ligand, TRV120023, in a dilated cardiomyopathy model.
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, 33 citations in OpenAlex.
- Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension.Journal of the American Heart Association · 2024Article
- Insights Into the Role of Angiotensin-II ATHypertension (Dallas, Tex. : 1979) · 2024Review
- Advances in the allostery of angiotensin II type 1 receptor.Cell & bioscience · 2023Review
- Pathophysiology and pharmacology of G protein-coupled receptors in the heart.Cardiovascular research · 2023Review
- Development of a Non-Peptide Angiotensin II Type 1 Receptor Ligand by Structural Modification of Olmesartan as a Biased Agonist.Biomedicines · 2023Article
- Pepducin ICL1-9-Mediated β2-Adrenergic Receptor-Dependent Cardiomyocyte Contractility Occurs in a GCardiovascular drugs and therapy · 2023Article
- Molecular Effects of Auto-Antibodies on Angiotensin II Type 1 Receptor Signaling and Cell Proliferation.International journal of molecular sciences · 2022Article
- β-Arrestin-Mediated Angiotensin II Type 1 Receptor Activation Promotes Pulmonary Vascular Remodeling in Pulmonary Hypertension.JACC. Basic to translational science · 2021Article
- Hypertrophic cardiomyopathy associated E22K mutation in myosin regulatory light chain decreases calcium-activated tension and stiffness and reduces myofilament CaThe FEBS journal · 2021Article
- Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes.International journal of molecular sciences · 2021Review
- Mechanisms of troponin release into serum in cardiac injury associated with COVID-19 patients.International journal of cardiology and cardiovascular diseases · 2021Article
- Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles.JACC. Basic to translational science · 2020Article
- The Role of β-Arrestin Proteins in Organization of Signaling and Regulation of the AT1 Angiotensin Receptor.Frontiers in endocrinology · 2019Review
- Pathogenic troponin T mutants with opposing effects on myofilament CaArchives of biochemistry and biophysics · 2019Article
- Mechanisms of signalling and biased agonism in G protein-coupled receptors.Nature reviews. Molecular cell biology · 2018Review
- Designer Approaches for G Protein-Coupled Receptor Modulation for Cardiovascular Disease.JACC. Basic to translational science · 2018Review
- Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.Physiological reviews · 2018Review
- Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?Drug discovery today · 2017Review
- Current topics in angiotensin II type 1 receptor research: Focus on inverse agonism, receptor dimerization and biased agonism.Pharmacological research · 2017Review
- The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling.Pharmacological reviews · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
aimsTherapeutic approaches to treat familial dilated cardiomyopathy (DCM), which is characterized by depressed sarcomeric tension and susceptibility to Ca(2+)-related arrhythmias, have been generally unsuccessful. Our objective in the present work was to determine the effect of the angiotensin II type 1 receptor (AT1R) biased ligand, TRV120023, on contractility of hearts of a transgenic mouse model of familial DCM with mutation in tropomyosin at position 54 (TG-E54K). Our rationale is based on previous studies, which have supported the hypothesis that biased G-protein-coupled receptor ligands, signalling via β-arrestin, increase cardiac contractility with no effect on Ca(2+) transients. Our previous work demonstrated that the biased ligand TRV120023 is able to block angiotensin-induced hypertrophy, while promoting an increase in sarcomere Ca(2+) response. METHODS AND
resultsWe tested the hypothesis that the depression in cardiac function associated with DCM can be offset by infusion of the AT1R biased ligand, TRV120023. We intravenously infused saline, TRV120023, or the unbiased ligand, losartan, for 15 min in TG-E54K and non-transgenic mice to obtain left ventricular pressure-volume relations. Hearts were analysed for sarcomeric protein phosphorylation. Results showed that the AT1R biased ligand increases cardiac performance in TG-E54K mice in association with increased myosin light chain-2 phosphorylation.
conclusionTreatment of mice with an AT1R biased ligand, acting via β-arrestin signalling, is able to induce an increase in cardiac contractility associated with an increase in ventricular myosin light chain-2 phosphorylation. AT1R biased ligands may prove to be a novel inotropic approach in familial DCM.
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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.