ArticleCardiovascular research2023
Inducible apelin receptor knockdown reduces differentiation efficiency and contractility of hESC-derived cardiomyocytes.
Article in Cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- Structural and functional determination of peptide versus small molecule ligand binding at the apelin receptor.Nature communications · 2024Article
- Advancing Cardiac Organoid Engineering Through Application of Biophysical Forces.IEEE reviews in biomedical engineering · 2024Article
- Co-localization of the sodium-glucose co-transporter-2 channel (SGLT-2) with endothelin ETA and ETB receptors in human cardiorenal tissue.Bioscience reports · 2024Article
- APJ as Promising Therapeutic Target of Peptide Analogues in Myocardial Infarction- and Hypertension-Induced Heart Failure.Pharmaceutics · 2023Review
- Article
- Expanding the apelin receptor pharmacological toolbox using novel fluorescent ligands.Frontiers in endocrinology · 2023Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsThe apelin receptor, a G protein-coupled receptor, has emerged as a key regulator of cardiovascular development, physiology, and disease. However, there is a lack of suitable human in vitro models to investigate the apelinergic system in cardiovascular cell types. For the first time we have used human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and a novel inducible knockdown system to examine the role of the apelin receptor in both cardiomyocyte development and to determine the consequences of loss of apelin receptor function as a model of disease. METHODS AND
resultsExpression of the apelin receptor and its ligands in hESCs and hESC-CMs was determined. hESCs carrying a tetracycline-inducible short hairpin RNA targeting the apelin receptor were generated using the sOPTiKD system. Phenotypic assays characterized the consequences of either apelin receptor knockdown before hESC-CM differentiation (early knockdown) or in 3D engineered heart tissues as a disease model (late knockdown). hESC-CMs expressed the apelin signalling system at a similar level to the adult heart. Early apelin receptor knockdown decreased cardiomyocyte differentiation efficiency and prolonged voltage sensing, associated with asynchronous contraction. Late apelin receptor knockdown had detrimental consequences on 3D engineered heart tissue contractile properties, decreasing contractility and increasing stiffness.
conclusionsWe have successfully knocked down the apelin receptor, using an inducible system, to demonstrate a key role in hESC-CM differentiation. Knockdown in 3D engineered heart tissues recapitulated the phenotype of apelin receptor down-regulation in a failing heart, providing a potential platform for modelling heart failure and testing novel therapeutic strategies.
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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.