Phospholemman Phosphorylation Regulates Vascular Tone, Blood Pressure, and Hypertension in Mice and Humans.

Animals Blood Pressure / drug effects Genomics / methods Humans Hypertension / drug therapy Male Membrane Proteins / pharmacology Mice Phosphoproteins / pharmacology Phosphorylation / physiology
Na/K ATPase blood hypertension phospholemman pressure vascular smooth muscle vascular tone

Journal

Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763

Informations de publication

Date de publication:
16 03 2021
Historique:
pubmed: 19 12 2020
medline: 24 12 2021
entrez: 18 12 2020
Statut: ppublish

Résumé

Although it has long been recognized that smooth muscle Na/K ATPase modulates vascular tone and blood pressure (BP), the role of its accessory protein phospholemman has not been characterized. The aim of this study was to test the hypothesis that phospholemman phosphorylation regulates vascular tone in vitro and that this mechanism plays an important role in modulation of vascular function and BP in experimental models in vivo and in humans. In mouse studies, phospholemman knock-in mice (PLM Phospholemman phosphorylation at Ser63 and Ser68 limited vascular constriction in response to phenylephrine. This effect was blocked by ouabain. Prevention of phospholemman phosphorylation in the PLM These studies demonstrate the importance of phospholemman phosphorylation in the regulation of vascular tone and BP and suggest a novel mechanism, and therapeutic target, for aging-induced essential hypertension in humans.

Sections du résumé

BACKGROUND
Although it has long been recognized that smooth muscle Na/K ATPase modulates vascular tone and blood pressure (BP), the role of its accessory protein phospholemman has not been characterized. The aim of this study was to test the hypothesis that phospholemman phosphorylation regulates vascular tone in vitro and that this mechanism plays an important role in modulation of vascular function and BP in experimental models in vivo and in humans.
METHODS
In mouse studies, phospholemman knock-in mice (PLM
RESULTS
Phospholemman phosphorylation at Ser63 and Ser68 limited vascular constriction in response to phenylephrine. This effect was blocked by ouabain. Prevention of phospholemman phosphorylation in the PLM
CONCLUSIONS
These studies demonstrate the importance of phospholemman phosphorylation in the regulation of vascular tone and BP and suggest a novel mechanism, and therapeutic target, for aging-induced essential hypertension in humans.

Identifiants

DOI: 10.1161/CIRCULATIONAHA.119.040557 PMID: 33334125 PMC: PMC7969167
pubmed: 33334125
doi: 10.1161/CIRCULATIONAHA.119.040557
pmc: PMC7969167
doi:

Substances chimiques

Membrane Proteins 0
Phosphoproteins 0
phospholemman 135541-82-1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1123-1138

Subventions

Organisme : British Heart Foundation
ID : RG/17/15/33106
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/18/2/34213
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/13/16/30199
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/14/58/30998
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/18/2/3421
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L016311/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/14/57/31138
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9521010
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/20/10427
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/18/6/34217
Pays : United Kingdom

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Auteurs

Andrii Boguslavskyi (A)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Sergiy Tokar (S)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Oleksandra Prysyazhna (O)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Olena Rudyk (O)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

David Sanchez-Tatay (D)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Hamish A L Lemmey (HAL)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Kim A Dora (KA)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Christopher J Garland (CJ)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Helen R Warren (HR)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Alexander Doney (A)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Colin N A Palmer (CNA)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Mark J Caulfield (MJ)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Julia Vlachaki Walker (J)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Jacqueline Howie (J)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

William Fuller (W)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

Michael J Shattock (MJ)

British Heart Foundation Centre of Research Excellence, King's College London, United Kingdom (A.B., S.T., O.P., O.R., D.S.-T., M.J.S.). Clinical Pharmacology, The William Harvey Research Institute (O.P., H.R.W., M.J.C.), National Institute for Health Research, Biomedical Research Centre (H.R.W., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. Department of Pharmacology, University of Oxford, United Kingdom (H.A.L.L., K.A.D., C.J.G.). Medicines Monitoring Unit, School of Medicine (A.D.), Division of Cardiovascular and Diabetes Medicine (C.N.A.), University of Dundee, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (J.V.W., J.H., W.F.).

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Phospholemman Phosphorylation Regulates...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Hémodynamique › Pression sanguine › Phospholemman Phosphorylation Regulates...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Phospholemman Phosphorylation Regulates...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Phospholemman Phosphorylation Regulates...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Hypertension artérielle › Phospholemman Phosphorylation Regulates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Phospholemman Phosphorylation Regulates...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Phospholemman Phosphorylation Regulates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Phospholemman Phosphorylation Regulates...
questionsmedicales.fr › Métabolisme › Phosphorylation › Phospholemman Phosphorylation Regulates...