Empagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model

Yihai Liu,1,2,* Mingyue Wu,1,* Biao Xu,1 Lina Kang1 1Department of Cardiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, People’s Republic of China; 2Department of Cardiology, Affiliated Drum Tower Hospital, Clinical College of Nanjing Medica...

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Autores principales:	Liu Y, Wu M, Xu B, Kang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	atherosclerosis sglt2i empagliflozin sympathetic activity raas Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ba026a2cfd9b44928fce8329a5e600ac
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spelling	oai:doaj.org-article:ba026a2cfd9b44928fce8329a5e600ac2021-12-02T18:20:42ZEmpagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model1178-7031https://doaj.org/article/ba026a2cfd9b44928fce8329a5e600ac2021-05-01T00:00:00Zhttps://www.dovepress.com/empagliflozin-alleviates-atherosclerosis-progression-by-inhibiting-inf-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Yihai Liu,1,2,* Mingyue Wu,1,* Biao Xu,1 Lina Kang1 1Department of Cardiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, People’s Republic of China; 2Department of Cardiology, Affiliated Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lina Kang; Biao XuDepartment of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, People’s Republic of ChinaEmail kanglina@njglyy.com; xubiao62@nju.edu.cnBackground: Recent clinical studies have revealed that sodium glucose co-transporter 2 inhibitors (SGLT2i) reduced cardiovascular events in type 2 diabetes. Here, we investigated whether empagliflozin, as a kind of SGLT2i, could alleviate atherosclerosis progression in non-diabetic mice.Methods: ApoE-/- mice were fed on a western diet for 12 weeks to induce atherosclerosis. The treatment group of mice was treated with drinking water containing empagliflozin (10mg/kg/day). On the 12th week, the whole aortas of each group were harvested. HE and Movat staining were performed for atherosclerotic lesion area and size. CD 68 and MCP-1 immunohistochemistry were used to evaluate inflammatory cell infiltration. Mouse serum lipid profiles (total cholesterol, triglyceride, low-density lipoprotein-C, and high-density lipoprotein-C), systemic inflammation level (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) and sympathetic activity (norepinephrine and neuropeptide Y) were measured by ELISA.Results: Empagliflozin could reduce the atherosclerotic lesion areas. Specifically, empagliflozin could significantly decreased inflammatory levels, RAAS and sympathetic activity in vivo. In vitro studies also showed that empagliflozin could inhibit IL-1β expression in oxLDL-treated macrophages by regulating NF-κB signaling.Conclusion: Empagliflozin could prevent atherosclerosis by repressing inflammation and sympathetic activity.Keywords: atherosclerosis, SGLT2i, empagliflozin, sympathetic activity, RAASLiu YWu MXu BKang LDove Medical Pressarticleatherosclerosissglt2iempagliflozinsympathetic activityraasPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 2277-2287 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	atherosclerosis sglt2i empagliflozin sympathetic activity raas Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	atherosclerosis sglt2i empagliflozin sympathetic activity raas Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Liu Y Wu M Xu B Kang L Empagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model
description	Yihai Liu,1,2,* Mingyue Wu,1,* Biao Xu,1 Lina Kang1 1Department of Cardiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, People’s Republic of China; 2Department of Cardiology, Affiliated Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lina Kang; Biao XuDepartment of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, People’s Republic of ChinaEmail kanglina@njglyy.com; xubiao62@nju.edu.cnBackground: Recent clinical studies have revealed that sodium glucose co-transporter 2 inhibitors (SGLT2i) reduced cardiovascular events in type 2 diabetes. Here, we investigated whether empagliflozin, as a kind of SGLT2i, could alleviate atherosclerosis progression in non-diabetic mice.Methods: ApoE-/- mice were fed on a western diet for 12 weeks to induce atherosclerosis. The treatment group of mice was treated with drinking water containing empagliflozin (10mg/kg/day). On the 12th week, the whole aortas of each group were harvested. HE and Movat staining were performed for atherosclerotic lesion area and size. CD 68 and MCP-1 immunohistochemistry were used to evaluate inflammatory cell infiltration. Mouse serum lipid profiles (total cholesterol, triglyceride, low-density lipoprotein-C, and high-density lipoprotein-C), systemic inflammation level (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) and sympathetic activity (norepinephrine and neuropeptide Y) were measured by ELISA.Results: Empagliflozin could reduce the atherosclerotic lesion areas. Specifically, empagliflozin could significantly decreased inflammatory levels, RAAS and sympathetic activity in vivo. In vitro studies also showed that empagliflozin could inhibit IL-1β expression in oxLDL-treated macrophages by regulating NF-κB signaling.Conclusion: Empagliflozin could prevent atherosclerosis by repressing inflammation and sympathetic activity.Keywords: atherosclerosis, SGLT2i, empagliflozin, sympathetic activity, RAAS
format	article
author	Liu Y Wu M Xu B Kang L
author_facet	Liu Y Wu M Xu B Kang L
author_sort	Liu Y
title	Empagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model
title_short	Empagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model
title_full	Empagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model
title_fullStr	Empagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model
title_full_unstemmed	Empagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model
title_sort	empagliflozin alleviates atherosclerosis progression by inhibiting inflammation and sympathetic activity in a normoglycemic mouse model
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/ba026a2cfd9b44928fce8329a5e600ac
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Empagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model

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