In one paragraphArticle in Cardiovascular research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
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2 · The registryThe trial behind it
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5 · Who and what moneyAuthors and funding
14 authors.
Marta MazzolaNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Houcheng WangNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.ORCID 0009-0004-3185-2588 Di LangDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, 1111 Highland Ave 8455 WIMR2, Madison, WI 53705, USA.ORCID 0000-0003-3318-4208 Marina BalychevaNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Navneet BhogalNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.ORCID 0000-0002-3135-4907 Jose L Sanchez-AlonsoNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.ORCID 0000-0003-2942-0079 Ivan DiakonovNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Carla LucarelliNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.ORCID 0000-0002-5321-1149 En-Chi LaiNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Prakash P PunjabiNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.ORCID 0000-0002-6587-1603 Michele MiragoliDepartment of Medicine and Surgery, University of Parma, Via Gramsci, 14 - 43124, Parma, Italy.ORCID 0000-0002-4058-4368 Giuseppe FaggianDepartment of Surgery, Dentistry, Pediatrics and Gynecology, Devision of Cardiac Surgery, University of Verona, 37129, Verona, Italy.
Alexey V GlukhovDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, 1111 Highland Ave 8455 WIMR2, Madison, WI 53705, USA.ORCID 0000-0003-2076-9688 Julia GorelikNational Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.ORCID 0000-0003-1148-9158 Funding
Functional Microdomains in the Heart's Pacemaker: A New Dimension of Cardiac RemodelingR01HL141214 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Alexey V Glukhov · 2018 to 2026
$3.8MMultiomics and Functional Characterization Establish Druggable Targets for PVC-Driven Idiopathic VFR01HL170521 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Lee Lochbaum Eckhardt, Eleonora Grandi · 2023 to 2026
$3.1MNeutral sphingomyelinase in the mechanical regulation of the heartR01HL182084 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Lee Lochbaum Eckhardt, Alexey V Glukhov · 2025 to 2026
$1.2MCell Identity and Functional Diversity of Sinoatrial Node Pacemaker Cell Subpopulations in the Physiology and Pathology of Cardiac PacemakingR01HL173344 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Di Lang · 2025 to 2026
$1.1MAmerican Heart Association 24SCEFIA1255230American Heart Association 846898British Heart Foundation BHF-RG/F/22/110081NHLBI NIH HHS R01 HL141214NHLBI NIH HHS R01 HL170521NHLBI NIH HHS R01 HL173344NHLBI NIH HHS R01 HL182084NIH HHS R01HL141214NIH HHS R01HL170521NIH HHS R01HL173344NIH HHS R01HL182084
6 · The paper itselfAbstract
aimsAdenosine, acting through A1 adenosine receptors (A1ARs), exerts anti-adrenergic effects by inhibiting β1-adrenergic receptor (β1AR)-mediated cyclic adenosine monophosphate (cAMP) production and contractility in the heart. While the functional interaction between A1ARs and β1ARs is well established in both atrial and ventricular myocytes, the subcellular compartmentalization of this crosstalk and how it is disrupted in heart failure (HF) remains incompletely understood. This study investigates the spatial confinement of A1AR-β1AR signalling within atrial microdomains and assesses how structural remodelling in HF alters this regulatory axis. METHODS AND
resultsQuantitative polymerase chain reaction (qPCR) analysis revealed that A1AR is the predominant adenosine receptor subtype in both rat and human atrial tissues. In healthy rat and mouse atrial myocytes, A1AR activation reduced β1AR-induced cAMP production and sarcomere shortening, with suppression of cAMP signals at sarcolemmal microdomains enriched in protein kinase A Type II. This was further supported by scanning ion conductance microscopy-guided scanning patch-clamp, which showed that A1AR suppressed β1AR-driven L-type Ca2+ channel activity at both T-tubule and crest membrane domains. In atrial myocytes isolated from failing rat and human hearts, A1AR-mediated inhibition of β1AR-induced cAMP production and contractility was impaired. Caveolar disruption by methyl-β-cyclodextrin in rat atrial myocytes or via cardiac-specific caveolin-3 (Cav3) knockout in mice abolished this A1AR-mediated inhibition. Notably, cholesterol repletion alone did not restore membrane cAMP regulation, whereas Cav3 overexpression rescued A1AR-dependent suppression, supporting a requirement for Cav3-dependent organization. In mouse atrial preparations isolated from failing hearts, high-resolution optical mapping showed that A1AR-mediated anti-adrenergic regulation of Ca2+ cycling was selectively lost in the intercaval region, correlating with the regional absence of T-tubule and downregulation of caveolae structures.
conclusionA1ARs provide anti-adrenergic restraint of β1AR signalling through Cav3-dependent membrane organization. In HF, regional caveolar disorganization uncouples this protective pathway, contributing to spatially heterogeneous Ca2+ dysregulation in the atrium.
Indexed as
CaveolaeHeart FailureMyocardial ContractionMyocytes, CardiacReceptor, Adenosine A1Receptors, Adrenergic, beta-1Adenosine A1 Receptor AgonistsAnimalsCalcium Channels, L-TypeCalcium SignalingCaveolin 3Cells, CulturedCyclic AMPDisease Models, AnimalHumansMaleAdenosine A1 Receptor AgonistsADRB1 protein, humanAdrb1 protein, mouseAdrb1 protein, ratCalcium Channels, L-TypeCav3 protein, mouseCav3 protein, ratCaveolin 3Cyclic AMPReceptor, Adenosine A1Receptors, Adrenergic, beta-1Adenosine A1 receptorCaveolaeFRET microscopyHeart failureOptical mappingT-tubulesΒ1-adrenergic receptor
Identifiers
PMID42336356
PMCPMC13355833
What Socratic holds
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