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

被引：39

作者：

Dimitriadis, Georgios K. ^{[1
,2
,3
,4
]}

Nasiri-Ansari, Narjes ^{[5
]}

Agrogiannis, Georgios ^{[6
]}

Kostakis, Ioannis D. ^{[7
]}

Randeva, Manpal S. ^{[3
]}

Nikiteas, Nikolaos ^{[8
]}

Patel, Vanlata H. ^{[1
]}

Kaltsas, Gregory ^{[9
]}

Papavassiliou, Athanasios G. ^{[5
]}

Randeva, Harpal S. ^{[1
,3
,4
,11
]}

Kassi, Eva ^{[5
,10
]}

机构：

[1] Univ Warwick, Warwick Med Sch, Div Translat & Expt Med Metab & Vasc Hlth, Coventry CV4 7AL, W Midlands, England

[2] Imperial Coll London, Div Endocrinol & Expt Med, Hammersmith Campus, London W12 0NN, England

[3] Univ Hosp Coventry & Warwickshire NHS Trust, WISDEM Ctr, Human Metab Res Unit, Coventry CV2 2DX, W Midlands, England

[4] Coventry Univ, Fac Hlth & Life Sci, Ctr Appl Biol & Exercise Sci, Coventry CV1 5FB, W Midlands, England

[5] Natl & Kapodistrian Univ Athens, Med Sch, Dept Biol Chem, Athens, Greece

[6] Natl & Kapodistrian Univ Athens, Med Sch, Lab Pathol Anat, Athens, Greece

[7] Guys & St Thomas NHS Fdn Trust, Guys Hosp, Dept Transplantat, London, England

[8] Natl & Kapodistrian Univ Athens, Med Sch, Lab Expt Surg & Surg Res NS Christeas, Athens, Greece

[9] Natl & Kapodistrian Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece

[10] Natl & Kapodistrian Univ Athens, Laiko Hosp, Dept Internal Med 1, Athens, Greece

[11] Aston Univ, Div Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2019年 / 494卷

关键词：

Empagliflozin; SGLT2i; Atherosclerosis; Inflammation; APOE knockout mice; GLUCOSE COTRANSPORTER 2; DIABETES-MELLITUS; BLOOD-PRESSURE; INHIBITOR;

D O I：

10.1016/j.mce.2019.110487

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：9

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