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P7 The role of G-protein-coupled receptor 55 (GPR55) in atherosclerosis – induced cardiovascular remodelling and dysfunction
  1. OJ Robertson-Gray1,
  2. SK Walsh1,
  3. AC Jönsson-Rylander2,
  4. E Ryberg2,
  5. CL Wainwright1
  1. 1Centre for Cardiometabolic Health Research, Robert Gordon University, Aberdeen, UK
  2. 2AstraZeneca R&D, CVMD Innovative Medicine, Bioscience, Mölndal, Sweden

Abstract

Mice lacking G-protein-coupled receptor 55 (GPR55) exhibit impaired contractile reserve and age-related systolic dysfunction, implying a role for this receptor in cardiac physiology/pathophysiology. To investigate the role of GPR55 in atherosclerosis-induced alterations in cardiac function, male and female, C57BL/6, ApoE-/-, GPR55-/- and ApoE-/-/GPR55-/- mice were fed a normal diet (ND) or high fat diet (HFD) for 12 weeks. Post-diet, indices of cardiac function were measured under anaesthesia via pressure-volume loop (PVL) analysis prior to harvesting blood and tissues for ex vivo analysis. Neither C57BL/6 nor GPR55-/- mice developed significant atherosclerotic plaques in the thoracic aorta, in response to HFD. ApoE-/- HFD mice demonstrated significant plaque deposition whereas ApoE-/-/GPR55-/- mice developed fewer plaques in response to HFD, suggesting GPR55 plays a detrimental role in atherogenesis. In contrast, while baseline systolic function (ejection fraction; EF and Emax) in ApoE-/- and GPR55-/- was similar to that in C57BL/6 mice, regardless of diet, high fat feeding in ApoE-/-/GPR55-/- mice caused a reduction systolic function, indicative of an important role for GPR55 in maintaining cardiac function in the hyperlipidaemic heart. Both ApoE-/- and ApoE-/-/GPR55-/- mice had similarly elevated LDL:HDL ratios, irrespective of diet, while GPR55-/- mice had similar LDL:HDL ratios to C57BL/6 mice that were unaffected by HFD. In conclusion, these results indicate that in the presence of high fat feeding, GPR55 has a complex role whereby it promotes atherosclerotic plaque development while maintaining systolic function. Neither of these role appears to be mediated by changes in plasma LDL:HDL ratios.

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