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GPR55 Deletion in Mice Leads to Age-Related Ventricular Dysfunction and Impaired Adrenoceptor-Mediated Inotropic Responses

G protein coupled receptor 55 (GPR55) is expressed throughout the body, and although its exact physiological function is unknown, studies have suggested a role in the cardiovascular system. In particular, GPR55 has been proposed as mediating the haemodynamic effects of a number of atypical cannabino...

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Autores principales: Walsh, Sarah K., Hector, Emma E., Andréasson, Anne-Christine, Jönsson-Rylander, Ann-Cathrine, Wainwright, Cherry L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183508/
https://www.ncbi.nlm.nih.gov/pubmed/25275556
http://dx.doi.org/10.1371/journal.pone.0108999
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author Walsh, Sarah K.
Hector, Emma E.
Andréasson, Anne-Christine
Jönsson-Rylander, Ann-Cathrine
Wainwright, Cherry L.
author_facet Walsh, Sarah K.
Hector, Emma E.
Andréasson, Anne-Christine
Jönsson-Rylander, Ann-Cathrine
Wainwright, Cherry L.
author_sort Walsh, Sarah K.
collection PubMed
description G protein coupled receptor 55 (GPR55) is expressed throughout the body, and although its exact physiological function is unknown, studies have suggested a role in the cardiovascular system. In particular, GPR55 has been proposed as mediating the haemodynamic effects of a number of atypical cannabinoid ligands; however this data is conflicting. Thus, given the incongruous nature of our understanding of the GPR55 receptor and the relative paucity of literature regarding its role in cardiovascular physiology, this study was carried out to examine the influence of GPR55 on cardiac function. Cardiac function was assessed via pressure volume loop analysis, and cardiac morphology/composition assessed via histological staining, in both wild-type (WT) and GPR55 knockout (GPR55(−/−)) mice. Pressure volume loop analysis revealed that basal cardiac function was similar in young WT and GPR55(−/−) mice. In contrast, mature GPR55(−/−) mice were characterised by both significant ventricular remodelling (reduced left ventricular wall thickness and increased collagen deposition) and systolic dysfunction when compared to age-matched WT mice. In particular, the load-dependent parameter, ejection fraction, and the load-independent indices, end-systolic pressure-volume relationship (ESPVR) and E (max), were all significantly (P<0.05) attenuated in mature GPR55(−/−) mice. Furthermore, GPR55(−/−) mice at all ages were characterised by a reduced contractile reserve. Our findings demonstrate that mice deficient in GPR55 exhibit maladaptive adrenergic signalling, as evidenced by the reduced contractile reserve. Furthermore, with age these mice are characterised by both significant adverse ventricular remodelling and systolic dysfunction. Taken together, this may suggest a role for GPR55 in the control of adrenergic signalling in the heart and potentially a role for this receptor in the pathogenesis of heart failure.
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spelling pubmed-41835082014-10-07 GPR55 Deletion in Mice Leads to Age-Related Ventricular Dysfunction and Impaired Adrenoceptor-Mediated Inotropic Responses Walsh, Sarah K. Hector, Emma E. Andréasson, Anne-Christine Jönsson-Rylander, Ann-Cathrine Wainwright, Cherry L. PLoS One Research Article G protein coupled receptor 55 (GPR55) is expressed throughout the body, and although its exact physiological function is unknown, studies have suggested a role in the cardiovascular system. In particular, GPR55 has been proposed as mediating the haemodynamic effects of a number of atypical cannabinoid ligands; however this data is conflicting. Thus, given the incongruous nature of our understanding of the GPR55 receptor and the relative paucity of literature regarding its role in cardiovascular physiology, this study was carried out to examine the influence of GPR55 on cardiac function. Cardiac function was assessed via pressure volume loop analysis, and cardiac morphology/composition assessed via histological staining, in both wild-type (WT) and GPR55 knockout (GPR55(−/−)) mice. Pressure volume loop analysis revealed that basal cardiac function was similar in young WT and GPR55(−/−) mice. In contrast, mature GPR55(−/−) mice were characterised by both significant ventricular remodelling (reduced left ventricular wall thickness and increased collagen deposition) and systolic dysfunction when compared to age-matched WT mice. In particular, the load-dependent parameter, ejection fraction, and the load-independent indices, end-systolic pressure-volume relationship (ESPVR) and E (max), were all significantly (P<0.05) attenuated in mature GPR55(−/−) mice. Furthermore, GPR55(−/−) mice at all ages were characterised by a reduced contractile reserve. Our findings demonstrate that mice deficient in GPR55 exhibit maladaptive adrenergic signalling, as evidenced by the reduced contractile reserve. Furthermore, with age these mice are characterised by both significant adverse ventricular remodelling and systolic dysfunction. Taken together, this may suggest a role for GPR55 in the control of adrenergic signalling in the heart and potentially a role for this receptor in the pathogenesis of heart failure. Public Library of Science 2014-10-02 /pmc/articles/PMC4183508/ /pubmed/25275556 http://dx.doi.org/10.1371/journal.pone.0108999 Text en © 2014 Walsh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Walsh, Sarah K.
Hector, Emma E.
Andréasson, Anne-Christine
Jönsson-Rylander, Ann-Cathrine
Wainwright, Cherry L.
GPR55 Deletion in Mice Leads to Age-Related Ventricular Dysfunction and Impaired Adrenoceptor-Mediated Inotropic Responses
title GPR55 Deletion in Mice Leads to Age-Related Ventricular Dysfunction and Impaired Adrenoceptor-Mediated Inotropic Responses
title_full GPR55 Deletion in Mice Leads to Age-Related Ventricular Dysfunction and Impaired Adrenoceptor-Mediated Inotropic Responses
title_fullStr GPR55 Deletion in Mice Leads to Age-Related Ventricular Dysfunction and Impaired Adrenoceptor-Mediated Inotropic Responses
title_full_unstemmed GPR55 Deletion in Mice Leads to Age-Related Ventricular Dysfunction and Impaired Adrenoceptor-Mediated Inotropic Responses
title_short GPR55 Deletion in Mice Leads to Age-Related Ventricular Dysfunction and Impaired Adrenoceptor-Mediated Inotropic Responses
title_sort gpr55 deletion in mice leads to age-related ventricular dysfunction and impaired adrenoceptor-mediated inotropic responses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183508/
https://www.ncbi.nlm.nih.gov/pubmed/25275556
http://dx.doi.org/10.1371/journal.pone.0108999
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