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Mas receptor deficiency is associated with worsening of lipid profile and severe hepatic steatosis in ApoE knockout mice

Authors

  • A.R. Silva
  • E.C. Aguilar
  • J.I. Alvarez-Leite
  • R.F. da Silva
  • R.M.E. Arantes
  • M. Bader
  • N. Alenina
  • G. Pelli
  • S. Lenglet
  • K. Galan
  • F. Montecucco
  • F. Mach
  • S.H.S. Santos
  • R.A.S. Santos

Journal

  • American Journal of Physiology Regulatory Integrative and Comparative Physiology

Citation

  • Am J Physiol Regul Integr Comp Physiol 305 (11): R1323-R1330

Abstract

  • The classical renin-angiotensin system (RAS) pathway has been recently updated with the identification of additional molecules (such as ACE2, Ang-(1-7) and Mas receptor) that might improve some pathophysiological processes in chronic inflammatory diseases. In the present study, we focused on the potential protective role of Mas receptor activation on mouse lipid profile, liver steatosis and atherogenesis. Mas/ApoE-Double-Knockout (DKO) mice (based on C57BL/6 strain of 20 weeks of age) were fed under normal diet and compared with aged-matched Mas and ApoE single KO as well as wild type mice. Mas/ApoE double deficiency was associated with increased serum levels of atherogenic fractions of cholesterol, triglycerides and fasting glucose when compared to wild type or single KO. Serum levels of HDL or leptin in DKO were lower than other groups. Hepatic lipid content as well as ALT serum levels were increased in DKO as compared to wild type or single KO animals. Accordingly, the hepatic protein content of mediators related to atherosclerotic inflammation, such as PPARα and LXR, was altered in an adverse way in DKO as compared to ApoE KO. On the other hand, DKO mice did not display increased atherogenesis and intraplaque inflammation as compared to ApoE KO group. In conclusion, Mas deletion in ApoE knockout mice was associated with development of severe liver steatosis and dyslipidemia without affecting concomitant atherosclerosis. Mas receptor activation might represent a promising strategies for future treatments targeting both hepatic and metabolic alterations in chronic conditions clustering these disorders.


DOI

doi:10.1152/ajpregu.00249.2013