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References from Bridging the gap: combining GPCR-based drug discovery with iPSC-based cardiovascular disease modeling in a dish. Local targets link to admitted publications; unresolved targets remain external evidence.
Cardiac GPCRs: GPCR signaling in healthy and failing hearts
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G protein-coupled receptor signaling: transducers and effectors
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Diversity of the Gβγ complexes defines spatial and temporal bias of GPCR signaling
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G protein γ subunit, a hidden master regulator of GPCR signaling
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The expanding roles of Gβγ subunits in G protein-coupled receptor signaling and drug action
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Non-canonical G protein signaling
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Non-canonical signaling and localizations of heterotrimeric G proteins
10.1016/j.cellsig.2011.08.014 · 2012 · External reference
G Protein-Coupled Receptor Signaling Through β-Arrestin-Dependent Mechanisms
10.1097/fjc.0000000000000482 · 2017 · External reference
β-Arrestin-mediated receptor trafficking and signal transduction
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The β-Arrestins: Multifunctional Regulators of G Protein-coupled Receptors
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GPCR drug discovery: new agents, targets and indications
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What Is the Role of β-Adrenergic Signaling in Heart Failure?
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Functional Characterization of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells
10.3390/ijms23158507 · 2022 · External reference
Aberrant α-adrenergic hypertrophic response in cardiomyocytes from human induced pluripotent cells
10.1016/j.stemcr.2014.09.002 · 2014 · External reference
Cardiac α1A-adrenergic receptors: emerging protective roles in cardiovascular diseases
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AT1 receptor signaling pathways in the cardiovascular system
10.1016/j.phrs.2017.05.008 · 2017 · External reference
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Adrenergic and muscarinic receptors in the human heart
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Distribution and function of the muscarinic receptor subtypes in the cardiovascular system
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Cardiotoxic and Cardioprotective Features of Chronic β-Adrenergic Signaling
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Chronic β2-adrenergic receptor stimulation increases proliferation of human cardiac fibroblasts via an autocrine mechanism
10.1016/s0008-6363(02)00729-0 · 2003 · External reference
Decreased Catecholamine Sensitivity and β-Adrenergic-Receptor Density in Failing Human Hearts
10.1056/nejm198207223070401 · 1982 · External reference
Adenylyl cyclase and G protein receptor kinase expression during development of heart failure
1997 · External reference
Expression of β-arrestins and β-adrenergic receptor kinases in the failing human heart
10.1161/01.res.74.2.206 · 1994 · External reference
Altered expression of β-adrenergic receptor kinase and β1-adrenergic receptors in the failing human heart
10.1161/01.cir.87.2.454 · 1993 · External reference
β-adrenoceptors in cardiac disease
10.1016/0163-7258(93)90030-h · 1993 · External reference
Increase in myocardial Gi-proteins in heart failure
10.1016/s0140-6736(88)92601-3 · 1988 · External reference
Increase of Giα in human hearts with dilated but not ischemic cardiomyopathy
10.1161/01.cir.82.4.1249 · 1990 · External reference
The functional significance of genetic variation within the β-adrenoceptor
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β1- and β2-adrenoceptor polymorphisms and cardiovascular diseases
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The myocardium-protective Gly-49 variant of the β1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation
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β1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to β-blocker therapy
10.1097/01213011-200504000-00006 · 2005 · External reference
Role of β adrenergic receptor polymorphisms in heart failure: Systematic review and meta-analysis
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Unresolved reference
2009 · External reference
α1-adrenergic receptors in heart failure: the adaptive arm of the cardiac response to chronic catecholamine stimulation
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Unresolved reference
2013 · External reference
Comparison between α1 adrenoceptor-mediated and β adrenoceptor-mediated inotropic components elicited by norepinephrine in failing human ventricular muscle
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Cardiac-directed overexpression of wild-type α1B-adrenergic receptor induces dilated cardiomyopathy
2001 · External reference
Type 2 angiotensin II receptor is downregulated in cardiomyocytes of patients with heart failure
10.1016/s0008-6363(00)00008-0 · 2000 · External reference
AT1 and AT2 angiotensin receptor gene expression in human heart failure
10.1161/01.cir.95.5.1201 · 1997 · External reference
Angiotensin Type-1 Receptor A1166C Gene Polymorphism Correlates With Oxidative Stress Levels in Human Heart Failure
10.1161/01.hyp.0000222893.85662.cd · 2006 · External reference
Role of angiotensin II type I (AT1 A1166C) receptor polymorphism in susceptibility of left ventricular dysfunction
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Muscarinic receptors in the failing human heart
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Increased Myocardial Muscarinic Receptor Density in Idiopathic Dilated Cardiomyopathy
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Endothelin-1, Outcomes in Patients With Heart Failure and Reduced Ejection Fraction, and Effects of Dapagliflozin: Findings From DAPA-HF
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Plasma big endothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension
10.1016/0002-9149(93)90543-l · 1993 · External reference
Oleanolic Acid, a Novel Endothelin A Receptor Antagonist, Alleviated High Glucose-Induced Cardiomyocytes Injury
10.1142/s0192415x18500623 · 2018 · External reference
Endothelial Cell–Derived Endothelin-1 Promotes Cardiac Fibrosis in Diabetic Hearts Through Stimulation of Endothelial-to-Mesenchymal Transition
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Endothelin-1 induces hypertrophy with enhanced expression of muscle-specific genes in cultured neonatal rat cardiomyocytes
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Conditional Cardiac Overexpression of Endothelin-1 Induces Inflammation and Dilated Cardiomyopathy in Mice
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Activation of ETAR and ETBR in myocardial tissue characterizes heart failure induced by experimental autoimmune myocarditis
10.1186/s12872-023-03658-1 · 2024 · External reference
Small molecule disruption of Gβγ signaling inhibits the progression of heart failure
10.1161/circresaha.110.217075 · 2010 · External reference
Simultaneous adrenal and cardiac G-protein-coupled receptor-Gβγ inhibition halts heart failure progression
10.1016/j.jacc.2014.02.587 · 2014 · External reference
Pharmacological and Activated Fibroblast Targeting of Gβγ-GRK2 After Myocardial Ischemia Attenuates Heart Failure Progression
10.1016/j.jacc.2017.06.049 · 2017 · External reference
Gβγ subunits colocalize with RNA polymerase II and regulate transcription in cardiac fibroblasts
10.1016/j.jbc.2023.103064 · 2023 · External reference
Propranolol prevents the development of heart failure by restoring FKBP12.6-mediated stabilization of ryanodine receptor
10.1161/hc1102.105270 · 2002 · External reference
Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial
10.1016/s0140-6736(03)13800-7 · 2003 · External reference
β-Blocker Use and Health Status Among Patients With Heart Failure With Preserved Ejection Fraction
10.1001/jamanetworkopen.2025.29519 · 2025 · External reference
An Oral Selective α1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity
10.1016/j.jacbts.2016.10.006 · 2017 · External reference
An α1A Adrenergic Receptor Agonist Prevents Acute Doxorubicin Cardiomyopathy in Male Mice
10.1371/journal.pone.0168409 · 2017 · External reference
Targeting the renin-angiotensin-aldosterone system in heart failure
10.1038/nrcardio.2012.196 · 2013 · External reference
Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study
10.1161/hypertensionaha.120.16667 · 2021 · External reference
Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension
10.7326/0003-4819-148-1-200801010-00189 · 2008 · External reference
or Both in Patients at High Risk for Vascular Events
10.1056/nejmoa0801317 · 2008 · External reference
Spironolactone for Heart Failure with Preserved Ejection Fraction
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Unresolved reference
2017 · External reference
Randomized, double-blind, placebo-controlled study of sitaxsentan to improve impaired exercise tolerance in patients with heart failure and a preserved ejection fraction
10.1016/j.jchf.2013.12.002 · 2014 · External reference
Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study
10.1016/j.cardfail.2004.05.006 · 2005 · External reference
Unresolved reference
2016 · External reference
Dual ETA-ETB receptor antagonism improves metabolic syndrome-induced heart failure with preserved ejection fraction
10.1111/fcp.70006 · 2025 · External reference
Endothelin as a Treatment Target in Cardiovascular Diseases: A Recent Step Forward
10.31083/rcm45417 · 2025 · External reference
Aprocitentan: The First Endothelin Receptor Antagonist for Resistant Hypertension
2025 · External reference
Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives
10.3390/ijms19010210 · 2018 · External reference
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors
10.1016/j.cell.2006.07.024 · 2006 · External reference
Induction of pluripotent stem cells from adult human fibroblasts by defined factors
10.1016/j.cell.2007.11.019 · 2007 · External reference
Recent progress of iPSC technology in cardiac diseases
10.1007/s00204-021-03172-3 · 2021 · External reference
Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity
10.1038/nm.4087 · 2016 · External reference
Chronic Cardiotoxicity Assays Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs)
10.3390/ijms23063199 · 2022 · External reference
Cardiotoxicity Hazard and Risk Characterization of ToxCast Chemicals Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes from Multiple Donors
10.1021/acs.chemrestox.1c00203 · 2021 · External reference
The flaws and human harms of animal experimentation
10.1017/s0963180115000079 · 2015 · External reference
Poor Translatability of Biomedical Research Using Animals - A Narrative Review
10.1177/02611929231157756 · 2023 · External reference
Human heart-forming organoids recapitulate early heart and foregut development
10.1038/s41587-021-00815-9 · 2021 · External reference
Cardioids reveal self-organizing principles of human cardiogenesis
10.1016/j.cell.2021.04.034 · 2021 · External reference
Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease
10.1038/s41467-021-25329-5 · 2021 · External reference
Multi-chamber cardioids unravel human heart development and cardiac defects
10.1016/j.cell.2023.10.030 · 2023 · External reference
Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions
10.1038/s41467-024-52221-9 · 2024 · External reference
A humanized engineered heart tissue platform for cardiotoxicity assessment
10.1016/j.stemcr.2026.102856 · 2026 · External reference
Three-Dimensional iPSC-Based In Vitro Cardiac Models for Biomedical and Pharmaceutical Research Applications
10.3390/ijms251910690 · 2024 · External reference
Cardiopedia-Ligand: A ligand-receptor perturbation atlas of human cardiac organoid function and transcriptional state
10.1016/j.stem.2026.07.004 · 2026 · External reference
Fluorescence Spectroscopy of Low-Level Endogenous β-Adrenergic Receptor Expression at the Plasma Membrane of Differentiating Human iPSC-Derived Cardiomyocytes
10.3390/ijms231810405 · 2022 · External reference
A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization
10.1038/s41467-023-43999-1 · 2023 · External reference
Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes
10.1038/s41598-023-39525-4 · 2023 · External reference
Losartan protects human stem cell-derived cardiomyocytes from angiotensin II-induced alcoholic cardiotoxicity
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Unresolved reference
2020 · External reference
Ion Channel Expression and Characterization in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
10.1155/2018/6067096 · 2018 · External reference
Endothelin-1 influences mechanical properties and contractility of hiPSC derived cardiomyocytes resulting in diastolic dysfunction
10.1016/j.yjmcc.2024.07.004 · 2024 · External reference
Endothelin-1 induces myofibrillar disarray and contractile vector variability in hypertrophic cardiomyopathy-induced pluripotent stem cell-derived cardiomyocytes
10.1161/jaha.114.001263 · 2014 · External reference
Gene and MicroRNA Profiling of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells
10.1007/s12015-014-9582-4 · 2015 · External reference
Detecting and measuring of GPCR signaling - comparison of human induced pluripotent stem cells and immortal cell lines
2023 · External reference
β-Adrenergic Receptors: Not Always Outside-In
2026 · External reference
On the inference of ERK signaling dynamics from protein biosensor measurements
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Live-cell fluorescent biosensors for activated signaling proteins
10.1016/s0955-0674(02)00313-7 · 2002 · External reference
Live-cell measurements of kinase activity in single cells using translocation reporters
10.1038/nprot.2017.128 · 2018 · External reference
Quantitative approaches for studying G protein-coupled receptor signalling and pharmacology
10.1242/jcs.263434 · 2025 · External reference
Multiparameter in vitro assessment of compound effects on cardiomyocyte physiology using iPSC cells
10.1177/1087057112457590 · 2013 · External reference
Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy
10.1126/scitranslmed.3003552 · 2012 · External reference
Carvedilol Phenocopies PGC-1α Overexpression to Alleviate Oxidative Stress, Mitochondrial Dysfunction and Prevent Doxorubicin-Induced Toxicity in Human iPSC-Derived Cardiomyocytes
2023 · External reference
Antiarrhythmic Effects of Carvedilol and Flecainide in Cardiomyocytes Derived from Catecholaminergic Polymorphic Ventricular Tachycardia Patients
10.1155/2018/9109503 · 2018 · External reference
A human pluripotent stem cell model of catecholaminergic polymorphic ventricular tachycardia recapitulates patient-specific drug responses
10.1242/dmm.026823 · 2016 · External reference
Pathogenic KCNH2-G53S variant in the PAS domain influences the electrophysiological phenotype in long QT syndrome type 2
10.3389/fcvm.2025.1524909 · 2025 · External reference
Patient-Specific Induced Pluripotent Stem-Cell Models for Long-QT Syndrome
10.1056/nejmoa0908679 · 2010 · External reference
Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation
10.1093/eurheartj/ehr073 · 2011 · External reference
Exploring mutation specific β blocker pharmacology of the pathogenic late sodium channel current from patient-specific pluripotent stem cell myocytes derived from long QT syndrome mutation carriers
10.1080/19336950.2022.2106025 · 2022 · External reference
Propranolol Attenuates Late Sodium Current in a Long QT Syndrome Type 3-Human Induced Pluripotent Stem Cell Model
10.3389/fcell.2020.00761 · 2020 · External reference
Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids
10.1016/j.isci.2025.112005 · 2025 · External reference
Optical Tracking and Digital Quantification of Beating Behavior in Bioengineered Human Cardiac Organoids
10.3390/bios7030024 · 2017 · External reference
PIV-MyoMonitor: an accessible particle image velocimetry-based software tool for advanced contractility assessment of cardiac organoids
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Self-assembled chamber-like cardiac organoids for modeling cardiac chamber formation and cardiotoxicity assessment
10.1038/s41467-026-73822-6 · 2026 · External reference
Maturation of human cardiac organoids enables complex disease modeling and drug discovery
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Sacubitril/valsartan reduces proteasome activation and cardiomyocyte area in an experimental mouse model of hypertrophy
2024 · External reference
Evaluation of chronic drug-induced electrophysiological and cytotoxic effects using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)
10.3389/fphar.2023.1229960 · 2023 · External reference
Olmesartan Restores LMNA Function in Haploinsufficient Cardiomyocytes
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Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy
10.1038/s41586-019-1406-x · 2019 · External reference
Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells
10.1016/j.stemcr.2021.08.018 · 2021 · External reference
Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing
10.1016/j.biomaterials.2019.119741 · 2020 · External reference
Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications
10.1038/s41467-024-46928-y · 2024 · External reference
iPSC-derived cardiac organoids for drug cardiotoxicity evaluation and efficacy prediction in myocardial infarction and cardiac hypertrophy models
10.1186/s13287-026-05079-1 · 2026 · External reference
The arrhythmogenic potential of nerve agents and a cardiac safety profile of antidotes - A proof-of-concept study using human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM)
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Human embryonic and induced pluripotent stem cell-derived cardiomyocytes exhibit beat rate variability and power-law behavior
10.1161/circulationaha.111.045146 · 2012 · External reference
Does Enhanced Structural Maturity of hiPSC-Cardiomyocytes Better for the Detection of Drug-Induced Cardiotoxicity?
10.3390/biom13040676 · 2023 · External reference
Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium
10.1016/j.stemcr.2018.10.008 · 2018 · External reference
Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology
10.15252/emmm.201404757 · 2015 · External reference
Generating ring-shaped engineered heart tissues from ventricular and atrial human pluripotent stem cell-derived cardiomyocytes
10.1038/s41467-019-13868-x · 2020 · External reference
Promoting differentiation of human-induced pluripotent stem cells into sinoatrial node-like cells through programmed regulation of AMPK signalling pathway
2025 · External reference
Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies
10.3390/cells11233764 · 2022 · External reference
A soft and ultrasensitive force sensing diaphragm for probing cardiac organoids instantaneously and wirelessly
10.1038/s41467-022-34860-y · 2022 · External reference
Endothelin-1 and angiotensin II modulate rate and contraction amplitude in a subpopulation of mouse embryonic stem cell-derived cardiomyocyte-containing bodies
10.1016/j.scr.2010.09.001 · 2011 · External reference
Endothelin has potent direct inotropic and chronotropic effects in cultured heart cells
10.1097/00004872-198900076-00044 · 1989 · External reference
Postischemic antiarrhythmic effects of angiotensin-converting enzyme inhibitors. Role of suppression of endogenous endothelin secretion
10.1161/01.cir.94.7.1752 · 1996 · External reference
Contractile and Arrhythmic Effects of Endothelin Receptor Agonists in Human Heart In Vitro: Blockade with SB 2096701
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Endothelin-1-induced arrhythmogenic Ca2+ signaling is abolished in atrial myocytes of inositol-1,4,5-trisphosphate(IP3)-receptor type 2-deficient mice
10.1161/01.res.0000172556.05576.4c · 2005 · External reference
RNA expression profiling of human iPSC-derived cardiomyocytes in a cardiac hypertrophy model
10.1371/journal.pone.0108051 · 2014 · External reference
Robust generation of human-chambered cardiac organoids from pluripotent stem cells for improved modelling of cardiovascular diseases
10.1186/s13287-022-03215-1 · 2022 · External reference
Modeling heart failure by induced pluripotent stem cell-derived organoids
10.1016/j.bbadis.2025.167861 · 2025 · External reference
Vascular cells improve functionality of human cardiac organoids
10.1016/j.celrep.2023.112322 · 2023 · External reference
Genome-wide pan-GPCR cell libraries accelerate drug discovery
10.1016/j.apsb.2024.06.023 · 2024 · External reference
Ultrastructural maturation of human-induced pluripotent stem cell-derived cardiomyocytes in a long-term culture
10.1253/circj.cj-12-0987 · 2013 · External reference
Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells
10.1089/scd.2012.0490 · 2013 · External reference
Time-dependent evolution of functional vs. remodeling signaling in induced pluripotent stem cell-derived cardiomyocytes and induced maturation with biomechanical stimulation
10.1096/fj.15-280982 · 2016 · External reference
Age-Dependent Maturation of iPSC-CMs Leads to the Enhanced Compartmentation of β2AR-cAMP Signalling
10.3390/cells9102275 · 2020 · External reference
Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes
10.1016/j.celrep.2020.107925 · 2020 · External reference
Physiological calcium combined with electrical pacing accelerates maturation of human engineered heart tissue
10.1016/j.stemcr.2022.07.006 · 2022 · External reference
Substrate Stiffness Influences Structural and Functional Remodeling in Induced Pluripotent Stem Cell-Derived Cardiomyocytes
10.3389/fphys.2021.710619 · 2021 · External reference
Human heart organoids: current applications and future perspectives
10.1093/eurheartj/ehad841 · 2024 · External reference
Vascularized hiPSC-derived 3D cardiac microtissue on chip
10.1016/j.stemcr.2023.06.001 · 2023 · External reference
Heart and kidney organoids maintain organ-specific function in a microfluidic system
2023 · External reference
Engineering a multi-organ chip to explore heart-brain crosstalk in health and pathology
2026 · External reference
Why 90% of clinical drug development fails and how to improve it?
10.1016/j.apsb.2022.02.002 · 2022 · External reference
Clinical trial in a dish using iPSCs shows lovastatin improves endothelial dysfunction and cellular cross-talk in LMNA cardiomyopathy
10.1126/scitranslmed.aax9276 · 2020 · External reference
Clinical Trial in a Dish: Personalized Stem Cell-Derived Cardiomyocyte Assay Compared With Clinical Trial Results for Two QT-Prolonging Drugs
10.1111/cts.12674 · 2019 · External reference
