Empagliflozin improves primary haemodynamic parameters and attenuates the development of atherosclerosis in high fat diet fed APOE knockout mice. (20th August 2019)

• Record Type: Journal Article
• Authors: Dimitriadis, Georgios K.; Nasiri-Ansari, Narjes; Agrogiannis, Georgios; Kostakis, Ioannis D.; Randeva, Manpal S.; Nikiteas, Nikolaos; Patel, Vanlata H.; Kaltsas, Gregory; Papavassiliou, Athanasios G.; Randeva, Harpal S.; Kassi, Eva
• Is Part Of: Molecular and cellular endocrinology. Volume 494(2019)
• Publication Date: 2019-08-20
• Subjects: Empagliflozin -- SGLT2i -- Atherosclerosis -- Inflammation -- APOE knockout mice; SGLT1 sodium glucose co-transporter 1 -- SGLT2 sodium glucose co-transporter 2 -- SGLT2i sodium glucose co-transporter 2 inhibitor -- T2DM type 2 diabetes mellitus -- APOE(−/−) apolipoprotein E knockout Apo-E(−/−) -- CV cardiovascular -- CVD cardiovascular disease -- MCP-1 monocyte chemoattractant protein 1 -- CD68 cluster of differentiation 68 -- HR heart rate -- MMP-2 matrix metalloproteinase- 2 -- MMP-9 matrix metalloproteinase-9 -- TIMP-1 tissue inhibitor of metalloproteinases-1 -- TIMP-2 tissue inhibitor of metalloproteinases-2 -- IL-6 interleukin 6 -- ICAM-1 intercellular adhesion molecule 1 -- VCAM-1 vascular cell adhesion molecule 1 -- Empa empagliflozin -- ECM extracellular matrix -- HbA1c hemoglobin A1c -- Il-6 interleukin 6 -- HFD high fat diet -- DBP diastolic blood pressure -- SBP systolic blood pressure; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2019.110487
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Highlights: Empagliflozin reduces heart rate and diastolic blood pressure in APOE (−/−) mice. Empagliflozin reduces total cholesterol and increases HDL cholesterol. Empagliflozin reduces atherosclerotic lesion formation. Empagliflozin reduces VCAM-1 and MCP-1 inflammatory molecule expression.