Empagliflozin improves primary haemodynamic parameters and attenuates the development of atherosclerosis in high fat diet fed APOE knockout mice

  • Mol Cell Endocrinol. 2019 Aug 20;494:110487. doi: 10.1016/j.mce.2019.110487.
Georgios K Dimitriadis  1 ,  Narjes Nasiri-Ansari  2 ,  Georgios Agrogiannis  3 ,  Ioannis D Kostakis  4 ,  Manpal S Randeva  5 ,  Nikolaos Nikiteas  6 ,  Vanlata H Patel  7 ,  Gregory Kaltsas  8 ,  Athanasios G Papavassiliou  2 ,  Harpal S Randeva  9 ,  Eva Kassi  10
Affiliations
  • 1. Division of Translational and Experimental Medicine-Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK; Division of Endocrinology and Experimental Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK; Human Metabolism Research Unit, WISDEM Centre, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, UK; Centre of Applied Biological & Exercise Sciences, Faculty of Health & Life Sciences, Coventry University, Coventry, CV1 5FB, UK.
  • 2. Department of Biological Chemistry, National and Kapodistrian Univer-sity of Athens Medical School, Athens, Greece.
  • 3. Laboratory of Pathological Anatomy, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
  • 4. Department of Transplantation, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • 5. Human Metabolism Research Unit, WISDEM Centre, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, UK.
  • 6. Laboratory for Experimental Surgery and Surgical Research "N.S. Christeas", Medical School, National and Kapodistrian University of Athens, Athens, Greece.
  • 7. Division of Translational and Experimental Medicine-Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
  • 8. 1(st) Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Greece.
  • 9. Division of Translational and Experimental Medicine-Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK; Human Metabolism Research Unit, WISDEM Centre, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, UK; Centre of Applied Biological & Exercise Sciences, Faculty of Health & Life Sciences, Coventry University, Coventry, CV1 5FB, UK; Division of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK. Electronic address: [email protected].
  • 10. Department of Biological Chemistry, National and Kapodistrian Univer-sity of Athens Medical School, Athens, Greece; 1(st) Department of Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: [email protected].
PMID: 31195080 DOI: 10.1016/j.mce.2019.110487
Abstract

The effects of long-term treatment with empagliflozin on biochemical and immunohistochemical markers related to atherosclerosis and atherosclerosis development in the aorta of Apolipoprotein E knockout [Apo-E (-/-)] mice were evaluated in this study. Empagliflozin-treated mice had lower total Cholesterol (P < 0.05), fasting glucose (P < 0.01), heart rate (P < 0.01) and diastolic blood pressure (DBP) (P < 0.05) compared to controls. Histomorphometry revealed reduced atherosclerotic lesion progress approaching statistical significance (P = 0.06) and approximately 50% wider lumen area for the Empagliflozin treated mice group. Although empagliflozin significantly reduced Vcam-1 and Mcp-1 (P < 0.05, P < 0.01, respectively) and marginally induced TIMP-1 and TIMP-2 mRNA expression (P < 0.08, P = 0.1 respectively), immunohistochemistry revealed a marginal reduction in VCAM-1 and MMP-9 (P = 0.1) without affecting the expression of TIMP-2 and MCP-1 in atherosclerotic lesions. Empagliflozin improves primary haemodynamic parameters and attenuates the progression of atherosclerosis by reducing hyperlipidemia and hyperglycemia, while direct actions in aorta vessel mediated via SGLT-1 are strongly hypothesized.

Keywords
APOE knockout mice; Atherosclerosis; Empagliflozin; Inflammation; SGLT2i.
Products