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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.

Authors

Sarah K. Walsh

Emma E. Hector

Anne-Christine Andréasson

Ann-Cathrine Jönsson-Rylander



Abstract

G protein coupled receptor 55 (GPR55) is expressed throughout the body and, although its exact physiological function is unknown, studies have suggested that it has 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.

Citation

WALSH, S.K., HECTOR, E.E., ANDREASSON, A.-C., JONSSON-RYLANDER, A.-C. and WAINWRIGHT, C. L. 2014. GPR55 deletion in mice leads to age-related ventricular dysfunction and impaired adrenoceptor-mediated inotropic responses. PLoS ONE [online], 9(10), article number e108999. Available from: https://doi.org/10.1371/journal.pone.0108999

Journal Article Type Article
Acceptance Date Sep 5, 2014
Online Publication Date Oct 2, 2014
Publication Date Dec 31, 2014
Deposit Date Oct 6, 2014
Publicly Available Date Oct 6, 2014
Journal PLoS ONE
Print ISSN 1932-6203
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 10
Article Number e108999
DOI https://doi.org/10.1371/journal.pone.0108999
Keywords G protein coupled receptor 55 (GPR55); Cardiovascular system; Pressure volume loop analysis; Heart failure
Public URL http://hdl.handle.net/10059/1054

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