Therapeutic Inhibition of Acid-Sensing Ion Channel 1a Recovers Heart Function After Ischemia-Reperfusion Injury.

Acid Sensing Ion Channels / biosynthesis Animals Cells, Cultured Female Humans Induced Pluripotent Stem Cells / drug effects Isolated Heart Preparation / methods Male Mice Mice, Knockout Myocardial Ischemia / genetics Myocardial Reperfusion Injury / genetics Myocytes, Cardiac / drug effects Polymorphism, Single Nucleotide / physiology Recovery of Function / drug effects Spider Venoms / pharmacology
acid sensing ion channels acidosis heart transplantation ischemia myocardial infarction

Journal

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

Informations de publication

Date de publication:
21 09 2021
Historique:
pubmed: 16 7 2021
medline: 29 12 2021
entrez: 15 7 2021
Statut: ppublish

Résumé

Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly affects cardiac function. We used genetic and pharmacologic methods to investigate the role of acid-sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole-organ level. Human induced pluripotent stem cell-derived cardiomyocytes as well as ex vivo and in vivo models of IRI were used to test the efficacy of ASIC1a inhibitors as pre- and postconditioning therapeutic agents. Analysis of human complex trait genetics indicates that variants in the Our data provide compelling evidence for a novel pharmacologic strategy involving ASIC1a blockade as a cardioprotective therapy to improve the viability of hearts subjected to IRI.

Sections du résumé

BACKGROUND
Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly affects cardiac function.
METHODS
We used genetic and pharmacologic methods to investigate the role of acid-sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole-organ level. Human induced pluripotent stem cell-derived cardiomyocytes as well as ex vivo and in vivo models of IRI were used to test the efficacy of ASIC1a inhibitors as pre- and postconditioning therapeutic agents.
RESULTS
Analysis of human complex trait genetics indicates that variants in the
CONCLUSIONS
Our data provide compelling evidence for a novel pharmacologic strategy involving ASIC1a blockade as a cardioprotective therapy to improve the viability of hearts subjected to IRI.

Identifiants

DOI: 10.1161/CIRCULATIONAHA.121.054360 PMID: 34264749
pubmed: 34264749
doi: 10.1161/CIRCULATIONAHA.121.054360
doi:

Substances chimiques

ASIC1 protein, human 0
Acid Sensing Ion Channels 0
Spider Venoms 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

947-960

Commentaires et corrections

Type : ErratumIn

Auteurs

Meredith A Redd (MA)

Institute for Molecular Bioscience (M.A.R., N.J.S., H.S.C., C.Y.C., X.C., Y.S., M.A.H.A., G.F.K., N.J.P.), The University of Queensland, St Lucia, Australia.
Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Brisbane, Australia (M.A.R., L.E.S.H., J.Y.S., J.F.F.).
ORCID: 0000-0002-4143-1726

Sarah E Scheuer (SE)

Victor Chang Cardiac Research Institute, Sydney, Australia (S.E.S., L.G., M.H., J.E.V., Y.J., P.S.M.).
Cardiopulmonary Transplant Unit (S.E.S., Y.J., P.S.M.), St Vincent's Hospital, Sydney, Australia.
Faculty of Medicine, University of New South Wales, Sydney, Australia (S.E.S., M.H., J.E.V., Y.J., P.S.M.).

Natalie J Saez (NJ)

Institute for Molecular Bioscience (M.A.R., N.J.S., H.S.C., C.Y.C., X.C., Y.S., M.A.H.A., G.F.K., N.J.P.), The University of Queensland, St Lucia, Australia.
Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science (N.J.S., G.F.K.), The University of Queensland, St Lucia, Australia.

Yusuke Yoshikawa (Y)

School of Biomedical Sciences (Y.Y., M.E.R., W.G.T.), The University of Queensland, St Lucia, Australia.

Han Sheng Chiu (HS)

Institute for Molecular Bioscience (M.A.R., N.J.S., H.S.C., C.Y.C., X.C., Y.S., M.A.H.A., G.F.K., N.J.P.), The University of Queensland, St Lucia, Australia.

Ling Gao (L)

Victor Chang Cardiac Research Institute, Sydney, Australia (S.E.S., L.G., M.H., J.E.V., Y.J., P.S.M.).

Mark Hicks (M)

Victor Chang Cardiac Research Institute, Sydney, Australia (S.E.S., L.G., M.H., J.E.V., Y.J., P.S.M.).
Department of Pharmacology (M.H.), St Vincent's Hospital, Sydney, Australia.
Faculty of Medicine, University of New South Wales, Sydney, Australia (S.E.S., M.H., J.E.V., Y.J., P.S.M.).

Jeanette E Villanueva (JE)

Victor Chang Cardiac Research Institute, Sydney, Australia (S.E.S., L.G., M.H., J.E.V., Y.J., P.S.M.).
Faculty of Medicine, University of New South Wales, Sydney, Australia (S.E.S., M.H., J.E.V., Y.J., P.S.M.).

Yashutosh Joshi (Y)

Victor Chang Cardiac Research Institute, Sydney, Australia (S.E.S., L.G., M.H., J.E.V., Y.J., P.S.M.).
Cardiopulmonary Transplant Unit (S.E.S., Y.J., P.S.M.), St Vincent's Hospital, Sydney, Australia.
Faculty of Medicine, University of New South Wales, Sydney, Australia (S.E.S., M.H., J.E.V., Y.J., P.S.M.).
ORCID: 0000-0003-0881-2436

Chun Yuen Chow (CY)

Institute for Molecular Bioscience (M.A.R., N.J.S., H.S.C., C.Y.C., X.C., Y.S., M.A.H.A., G.F.K., N.J.P.), The University of Queensland, St Lucia, Australia.
ORCID: 0000-0003-2861-5843

Gabriel Cuellar-Partida (G)

The University of Queensland Diamantina Institute, Faculty of Medicine and Translational Research Institute, Woolloongabba, Australia (G.C.-P.).

Jason N Peart (JN)

School of Medical Science, Griffith University, Southport, Australia (J.N.P.).

Louise E See Hoe (LE)

Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Brisbane, Australia (M.A.R., L.E.S.H., J.Y.S., J.F.F.).
Faculty of Medicine, The University of Queensland, Brisbane, Australia (L.E.S.H., J.Y.S., J.F.F.).

Xiaoli Chen (X)

Institute for Molecular Bioscience (M.A.R., N.J.S., H.S.C., C.Y.C., X.C., Y.S., M.A.H.A., G.F.K., N.J.P.), The University of Queensland, St Lucia, Australia.

Yuliangzi Sun (Y)

Institute for Molecular Bioscience (M.A.R., N.J.S., H.S.C., C.Y.C., X.C., Y.S., M.A.H.A., G.F.K., N.J.P.), The University of Queensland, St Lucia, Australia.
ORCID: 0000-0001-9785-4261

Jacky Y Suen (JY)

Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Brisbane, Australia (M.A.R., L.E.S.H., J.Y.S., J.F.F.).
Faculty of Medicine, The University of Queensland, Brisbane, Australia (L.E.S.H., J.Y.S., J.F.F.).
ORCID: 0000-0002-0309-2524

Robert J Hatch (RJ)

Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia (R.J.H., B.R., S.M., S.P.).
ORCID: 0000-0001-7119-5990

Ben Rollo (B)

Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia (R.J.H., B.R., S.M., S.P.).

Di Xia (D)

Genome Innovation Hub (D.X.), The University of Queensland, St Lucia, Australia.
ORCID: 0000-0001-8058-5536

Mubarak A H Alzubaidi (MAH)

Institute for Molecular Bioscience (M.A.R., N.J.S., H.S.C., C.Y.C., X.C., Y.S., M.A.H.A., G.F.K., N.J.P.), The University of Queensland, St Lucia, Australia.

Snezana Maljevic (S)

Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia (R.J.H., B.R., S.M., S.P.).

Gregory A Quaife-Ryan (GA)

QIMR Berghofer Medical Research Institute, Brisbane, Australia (G.A.Q.-R., J.E.H.).
ORCID: 0000-0002-0012-9934

James E Hudson (JE)

QIMR Berghofer Medical Research Institute, Brisbane, Australia (G.A.Q.-R., J.E.H.).

Enzo R Porrello (ER)

Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, Australia (E.R.P.).
Department of Anatomy and Physiology, School of Biomedical Sciences, The University of Melbourne, Parkville, Australia (E.R.P.).
ORCID: 0000-0001-6105-7463

Melanie Y White (MY)

School of Medical Sciences, School of Life and Environmental Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, Australia (M.Y.W., S.J.C.).

Stuart J Cordwell (SJ)

School of Medical Sciences, School of Life and Environmental Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, Australia (M.Y.W., S.J.C.).

John F Fraser (JF)

Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Brisbane, Australia (M.A.R., L.E.S.H., J.Y.S., J.F.F.).
Faculty of Medicine, The University of Queensland, Brisbane, Australia (L.E.S.H., J.Y.S., J.F.F.).

Steven Petrou (S)

Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia (R.J.H., B.R., S.M., S.P.).

Melissa E Reichelt (ME)

School of Biomedical Sciences (Y.Y., M.E.R., W.G.T.), The University of Queensland, St Lucia, Australia.

Walter G Thomas (WG)

School of Biomedical Sciences (Y.Y., M.E.R., W.G.T.), The University of Queensland, St Lucia, Australia.

Glenn F King (GF)

Institute for Molecular Bioscience (M.A.R., N.J.S., H.S.C., C.Y.C., X.C., Y.S., M.A.H.A., G.F.K., N.J.P.), The University of Queensland, St Lucia, Australia.
Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science (N.J.S., G.F.K.), The University of Queensland, St Lucia, Australia.
ORCID: 0000-0002-2308-2200

Peter S Macdonald (PS)

Victor Chang Cardiac Research Institute, Sydney, Australia (S.E.S., L.G., M.H., J.E.V., Y.J., P.S.M.).
Cardiopulmonary Transplant Unit (S.E.S., Y.J., P.S.M.), St Vincent's Hospital, Sydney, Australia.
Faculty of Medicine, University of New South Wales, Sydney, Australia (S.E.S., M.H., J.E.V., Y.J., P.S.M.).
ORCID: 0000-0001-5378-2825

Nathan J Palpant (NJ)

Institute for Molecular Bioscience (M.A.R., N.J.S., H.S.C., C.Y.C., X.C., Y.S., M.A.H.A., G.F.K., N.J.P.), The University of Queensland, St Lucia, Australia.
ORCID: 0000-0002-9334-8107

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Classifications MeSH

Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Canaux ioniques sensibles à l'acidité › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Eucaryotes › Animaux › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Cellules › Cellules cultivées › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches pluripotentes induites › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Techniques d'investigation › Modèles animaux › Préparation de coeur isolé › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Maladies cardiovasculaires › Maladies vasculaires › Ischémie myocardique › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › États, signes et symptômes pathologiques › Processus pathologiques › Complications postopératoires › Lésion d'ischémie-reperfusion › Lésion de reperfusion myocardique › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Cellules › Cellules musculaires › Myocytes cardiaques › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Phénomènes biologiques › Récupération fonctionnelle › Therapeutic Inhibition of Acid-Sensing Ion...
Recherchemedicale.com › Facteurs biologiques › Toxines biologiques › Venins › Venins d'arthropode › Venins d'araignée › Therapeutic Inhibition of Acid-Sensing Ion...