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Title: Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis

Abstract

Activated vascular endothelium inflammation under persistent hyperlipidemia is the initial step of atherogenesis. ATP-binding cassette G1 (ABCG1) is a crucial factor maintaining sterol and lipid homeostasis by transporting cholesterol efflux to high-density lipoprotein. In this study, we investigated the protective effects of ABCG1 in endothelial inflammation activation during early-stage atherogenesis in mice and the underlying mechanisms. Endothelial cell (EC)-specific ABCG1 transgenic (EC-ABCG1-Tg) mice were generated and cross-bred with low-density lipoprotein receptor–deficient (Ldlr{sup −/−}) mice. After a 4-week Western-type diet, the mice were sacrificed for assessing atherosclerosis. Human umbilical vein ECs were treated with different flows, and ABCG1 was adenovirally overexpressed to investigate the mechanism in vitro. Compared with Ldlr{sup −/−} mouse aortas, EC-ABCG1-Tg/Ldlr{sup −/−} aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr{sup −/−} mouse aortic arch but not thoracic aorta was significantly reduced, which suggests a protective role of ABCG1 under atheroprone flow. In vitro, overexpression of ABCG1 attenuated EC activation caused by oscillatory shear stress. Overexpression of ABCG1 blunted cholesterol-activated ECs in vitro. In exploring the mechanisms of ABCG1 attenuating endothelial inflammation, we found that ABCG1 inhibited oscillatory flow-activated nuclear factor kappa B and NLRP3 inflammasome in ECs. ABCG1 may play a protective role in early-stage atherosclerosis bymore » reducing endothelial activation induced by oscillatory shear stress via suppressing the inflammatory response. - Highlights: • EC-ABCG1-Tg mice in a Ldlr{sup −/−} background showed decreased atherosclerosis. • Overexpression of ABCG1 in ECs decreased OSS-induced EC activation. • NLRP3 and NF-κB might be an underlying mechanism of ABCG1 protective role.« less

Authors:
 [1];  [2];  [3]; ; ; ;  [1];  [3];  [1];  [1];  [2];  [1]
  1. Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China)
  2. (China)
  3. Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China)
Publication Date:
OSTI Identifier:
22606160
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 477; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AORTA; ARTERIOSCLEROSIS; ATP; CHOLESTEROL; DIET; ENDOTHELIUM; HOMEOSTASIS; IN VITRO; INFLAMMATION; LIPOPROTEINS; LYMPHOKINES; MICE; MOLECULES; MONOCYTES; NITRIC OXIDE; RECEPTORS; SHEAR; VEINS

Citation Formats

Xue, Shanshan, Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800, Wang, Jiaxing, Zhang, Xu, Shi, Ying, Li, Bochuan, Bao, Qiankun, Pang, Wei, Ai, Ding, Zhu, Yi, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191, and He, Jinlong, E-mail: hejinlong@tmu.edu.cn. Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.06.050.
Xue, Shanshan, Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800, Wang, Jiaxing, Zhang, Xu, Shi, Ying, Li, Bochuan, Bao, Qiankun, Pang, Wei, Ai, Ding, Zhu, Yi, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191, & He, Jinlong, E-mail: hejinlong@tmu.edu.cn. Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis. United States. doi:10.1016/J.BBRC.2016.06.050.
Xue, Shanshan, Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800, Wang, Jiaxing, Zhang, Xu, Shi, Ying, Li, Bochuan, Bao, Qiankun, Pang, Wei, Ai, Ding, Zhu, Yi, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191, and He, Jinlong, E-mail: hejinlong@tmu.edu.cn. Fri . "Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis". United States. doi:10.1016/J.BBRC.2016.06.050.
@article{osti_22606160,
title = {Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis},
author = {Xue, Shanshan and Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800 and Wang, Jiaxing and Zhang, Xu and Shi, Ying and Li, Bochuan and Bao, Qiankun and Pang, Wei and Ai, Ding and Zhu, Yi and Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 and He, Jinlong, E-mail: hejinlong@tmu.edu.cn},
abstractNote = {Activated vascular endothelium inflammation under persistent hyperlipidemia is the initial step of atherogenesis. ATP-binding cassette G1 (ABCG1) is a crucial factor maintaining sterol and lipid homeostasis by transporting cholesterol efflux to high-density lipoprotein. In this study, we investigated the protective effects of ABCG1 in endothelial inflammation activation during early-stage atherogenesis in mice and the underlying mechanisms. Endothelial cell (EC)-specific ABCG1 transgenic (EC-ABCG1-Tg) mice were generated and cross-bred with low-density lipoprotein receptor–deficient (Ldlr{sup −/−}) mice. After a 4-week Western-type diet, the mice were sacrificed for assessing atherosclerosis. Human umbilical vein ECs were treated with different flows, and ABCG1 was adenovirally overexpressed to investigate the mechanism in vitro. Compared with Ldlr{sup −/−} mouse aortas, EC-ABCG1-Tg/Ldlr{sup −/−} aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr{sup −/−} mouse aortic arch but not thoracic aorta was significantly reduced, which suggests a protective role of ABCG1 under atheroprone flow. In vitro, overexpression of ABCG1 attenuated EC activation caused by oscillatory shear stress. Overexpression of ABCG1 blunted cholesterol-activated ECs in vitro. In exploring the mechanisms of ABCG1 attenuating endothelial inflammation, we found that ABCG1 inhibited oscillatory flow-activated nuclear factor kappa B and NLRP3 inflammasome in ECs. ABCG1 may play a protective role in early-stage atherosclerosis by reducing endothelial activation induced by oscillatory shear stress via suppressing the inflammatory response. - Highlights: • EC-ABCG1-Tg mice in a Ldlr{sup −/−} background showed decreased atherosclerosis. • Overexpression of ABCG1 in ECs decreased OSS-induced EC activation. • NLRP3 and NF-κB might be an underlying mechanism of ABCG1 protective role.},
doi = {10.1016/J.BBRC.2016.06.050},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 477,
place = {United States},
year = {Fri Aug 19 00:00:00 EDT 2016},
month = {Fri Aug 19 00:00:00 EDT 2016}
}