Mas receptor deficiency is associated with worsening of lipid profile and severe hepatic steatosis in ApoE-knockout mice
- Silva, Analina R. INCT-NanoBiofar, Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
- Aguilar, Edenil C. Department of Biochemistry, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
- Alvarez-Leite, Jacqueline I. Department of Biochemistry, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
- da Silva, Rafaela F. INCT-NanoBiofar, Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
- Arantes, Rosa M. E. Department of Pathology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
- Bader, Michael Max-Delbrück Center for Molecular Medicine, Berlin, Germany;
- Alenina, Natalia Max-Delbrück Center for Molecular Medicine, Berlin, Germany;
- Pelli, Graziano Cardiology Division, Faculty of Medicine, University of Geneva, Geneva, Switzerland;
- Lenglet, Sébastien Cardiology Division, Faculty of Medicine, University of Geneva, Geneva, Switzerland;
- Galan, Katia Cardiology Division, Faculty of Medicine, University of Geneva, Geneva, Switzerland;
- Montecucco, Fabrizio First Medical Clinic, Laboratory of Phagocyte Physiopathology and Inflammation, Department of Internal Medicine, University of Genoa, Genoa, Italy; and
- Mach, François Cardiology Division, Faculty of Medicine, University of Geneva, Geneva, Switzerland;
- Santos, Sérgio H. S. Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
- Santos, Robson A. S. INCT-NanoBiofar, Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
Published in:
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. - American Physiological Society. - 2013, vol. 305, no. 11, p. R1323-R1330
English
The classical renin-angiotensin system pathway has been recently updated with the identification of additional molecules [such as angiotensin converting enzyme 2, 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/apolipoprotein E (ApoE)-double-knockout (DKO) mice (based on C57BL/6 strain of 20 wk of age) were fed under normal diet and compared with aged-matched Mas and ApoE-single-knockout (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 compared with wild-type or single KO. Serum levels of HDL or leptin in DKO were lower than in other groups. Hepatic lipid content as well as alanine aminotransferase serum levels were increased in DKO compared with wild-type or single-KO animals. Accordingly, the hepatic protein content of mediators related to atherosclerotic inflammation, such as peroxisome proliferator-activated receptor-α and liver X receptor, was altered in an adverse way in DKO compared with ApoE-KO. On the other hand, DKO mice did not display increased atherogenesis and intraplaque inflammation compared with ApoE-KO group. In conclusion, Mas deletion in ApoE-KO mice was associated with development of severe liver steatosis and dyslipidemia without affecting concomitant atherosclerosis. Mas receptor activation might represent promising strategies for future treatments targeting both hepatic and metabolic alterations in chronic conditions clustering these disorders.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1152/ajpregu.00249.2013
- ISSN 0363-6119
- Persistent URL
- https://sonar.rero.ch/global/documents/53193
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