Evidence map›Paper›PMID 39355927›Full record

ArticleCirculation2024

Essential Role of the RIα Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development.

Ibrahim Bedioune, Marine Gandon-Renard, Matthieu Dessillons, Aurélien Barthou, Audrey Varin, Delphine Mika, Saïd Bichali, Joffrey Cellier, Patrick Lechène, Sarah Karam and 14 more

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Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

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5citing papers in PubMed

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5 citing papers in PubMed.

Plant-Derived Bioactive Ingredients for Osteoporosis and Bone Regeneration: Mechanisms, Pharmacology, and Delivery Strategies.Cells · 2026
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The Small Molecule H89 Facilitates Mesenchymal Stem Cell-derived Extracellular Vesicle Release and Optimizes Therapeutic Efficacy in Liver Regeneration.Journal of extracellular vesicles · 2026
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Levistolide A Alleviates Myocardial Ischemia-Reperfusion Injury Partly by Improving Calcium Homeostasis via the ADORA2B/cAMP/PKA/PLB/SERCA2α Signaling Axis.Current issues in molecular biology · 2026
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Crustacean Protein Kinases A and C: Bioinformatic Characterization in Decapods and Other Non-Model Organisms.International journal of molecular sciences · 2025
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The role of A-kinase anchoring proteins in cardiovascular diseases and recent advances.Frontiers in cell and developmental biology · 2025
Review

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24 authors.

Ibrahim Bedioune *Université Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.

Marine Gandon-Renard *Université Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0002-4862-036X

Matthieu Dessillons *Université Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.

Aurélien Barthou *Université Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.

Audrey VarinUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0009-0000-1709-2333

Delphine MikaUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0003-2895-7173

Saïd BichaliUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0003-2220-6061

Joffrey CellierUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0003-2667-4639

Patrick LechèneUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0002-9194-0000

Sarah KaramUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.

Maya DiaUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0001-6531-9176

Susana GomezUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0002-4890-0548

Walma Pereira de VasconcelosUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.

Françoise Mercier-NoméUniversité Paris-Saclay, Inserm, UMS IPSIT (F.M.-N.), Orsay, France.ORCID 0000-0002-9515-7232

Philippe MateoUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0009-0005-1631-4615

Audrey DubourgUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0002-0213-1261

Constantine A StratakisHuman Genetics and Precision Medicine, IMBB, FORTH, Heraklion, Crete, Greece (C.A.S.).ORCID 0000-0002-4058-5520

Jean-Jacques MercadierUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0002-7398-0201

Jean-Pierre BenitahUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0002-9866-9081

Vincent AlgalarrondoUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0001-5971-1235

Jérôme LeroyUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0001-5168-0606

Rodolphe FischmeisterUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0003-2086-9865

Ana-Maria GomezUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0003-0009-2884

Grégoire VandecasteeleUniversité Paris-Saclay, Inserm, Signaling and Cardiovascular Pathophysiology, UMR-S1180 (I.B., M.G.-R., M.D., A.B., A.V., D.M., S.B., J.C., P.L., S.K., M.D., S.G., W.P.d.V., P.M., A.D., J.-J.M., J.-P.B., V.A., J.L., R.F., A.-M.G., G.V.), Orsay, France.ORCID 0000-0002-4046-4171

Funding

Ryanodine Receptors, Calcium-dependent Arrhythmias & HCMR01HL055438 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI VALDIVIA, HECTOR H · 1996 to 2023

$8.0M

NHLBI NIH HHS R01 HL055438

6 · The paper itself

Abstract

backgroundThe heart expresses 2 main subtypes of cAMP-dependent protein kinase (PKA; type I and II) that differ in their regulatory subunits, RIα and RIIα. Embryonic lethality of RIα knockout mice limits the current understanding of type I PKA function in the myocardium. The objective of this study was to test the role of RIα in adult heart contractility and pathological remodeling.

methodsWe measured PKA subunit expression in human heart and developed a conditional mouse model with cardiomyocyte-specific knockout of RIα (RIα-icKO). Myocardial structure and function were evaluated by echocardiography, histology, and ECG and in Langendorff-perfused hearts. PKA activity and cAMP levels were determined by immunoassay, and phosphorylation of PKA targets was assessed by Western blot. L-type Ca

resultsRIα protein was decreased by 50% in failing human heart with ischemic cardiomyopathy and by 75% in the ventricles and in VMs from RIα-icKO mice but not in atria or sinoatrial node. Basal PKA activity was increased ≈3-fold in RIα-icKO VMs. In young RIα-icKO mice, left ventricular ejection fraction was increased and the negative inotropic effect of propranolol was prevented, whereas heart rate and the negative chronotropic effect of propranolol were not modified. Phosphorylation of phospholamban, ryanodine receptor, troponin I, and cardiac myosin-binding protein C at PKA sites was increased in propranolol-treated RIα-icKO mice. Hearts from RIα-icKO mice were hypercontractile, associated with increased

conclusionsThese results identify RIα as a key negative regulator of cardiac contractile function, arrhythmia, and pathological remodeling.

Indexed as

Cyclic AMP-Dependent Protein Kinase RIalpha SubunitHeart FailureMice, KnockoutMyocardial ContractionMyocytes, CardiacAnimalsCalcium-Binding ProteinsCalcium Channels, L-TypeCalcium SignalingCyclic AMPCyclic AMP-Dependent Protein KinasesFemaleHumansMaleMicePhospholambanCalcium-Binding ProteinsCalcium Channels, L-TypeCyclic AMPCyclic AMP-Dependent Protein Kinase RIalpha SubunitCyclic AMP-Dependent Protein KinasesPhospholambanarrhythmias, cardiaccalciumcyclic AMP-dependent protein kinasesexcitation contraction couplingheartheart failureprotein kinases

Identifiers

PMID39355927

DOI10.1161/CIRCULATIONAHA.124.068858

PMCPMC11649463

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