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:	Sarah K Walsh, Emma E Hector, Anne-Christine Andréasson, Ann-Cathrine Jönsson-Rylander, Cherry L Wainwright
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dd26c54342f04552a5b6c5045d338fcb
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spelling	oai:doaj.org-article:dd26c54342f04552a5b6c5045d338fcb2021-11-25T05:58:08ZGPR55 deletion in mice leads to age-related ventricular dysfunction and impaired adrenoceptor-mediated inotropic responses.1932-620310.1371/journal.pone.0108999https://doaj.org/article/dd26c54342f04552a5b6c5045d338fcb2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108999https://doaj.org/toc/1932-6203G 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 Emax, 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.Sarah K WalshEmma E HectorAnne-Christine AndréassonAnn-Cathrine Jönsson-RylanderCherry L WainwrightPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e108999 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah K Walsh Emma E Hector Anne-Christine Andréasson Ann-Cathrine Jönsson-Rylander Cherry L Wainwright GPR55 deletion in mice leads to age-related ventricular dysfunction and impaired adrenoceptor-mediated inotropic responses.
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 Emax, 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.
format	article
author	Sarah K Walsh Emma E Hector Anne-Christine Andréasson Ann-Cathrine Jönsson-Rylander Cherry L Wainwright
author_facet	Sarah K Walsh Emma E Hector Anne-Christine Andréasson Ann-Cathrine Jönsson-Rylander Cherry L Wainwright
author_sort	Sarah K Walsh
title	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_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_sort	gpr55 deletion in mice leads to age-related ventricular dysfunction and impaired adrenoceptor-mediated inotropic responses.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/dd26c54342f04552a5b6c5045d338fcb
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GPR55 deletion in mice leads to age-related ventricular dysfunction and impaired adrenoceptor-mediated inotropic responses.

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