2. Academic Validation
  3. Empagliflozin improves primary haemodynamic parameters and attenuates the development of atherosclerosis in high fat diet fed APOE knockout mice

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

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.

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