Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis.
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(-/-)) 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(-/-) mouse aortas, EC-ABCG1-Tg/Ldlr(-/-) aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr(-/-) 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.
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China; Department of Pediatrics, Baodi District People's Hospital of Tianjin City, Tianjin, 301800, China.
Shanshan
S
Xue
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191, China.
Jiaxing
J
Wang
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.
Xu
X
Zhang
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.
Ying
Y
Shi
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.
Bochuan
B
Li
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.
Qiankun
Q
Bao
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191, China.
Wei
W
Pang
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.
Ding
D
Ai
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China; Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191, China.
Yi
Y
Zhu
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China. Electronic address: hejinlong@tmu.edu.cn.
Jinlong
J
He
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001018:Aortic Diseases / Q000503:physiopathology*; D050197:Atherosclerosis / Q000503:physiopathology*; D001683:Biological Clocks; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000503:physiopathology*; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D033081:Shear Strength; D013314:Stress, Mechanical
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1
ABCG1; Atherosclerosis; Cholesterol; Endothelial activation; Shear stress