scholarly journals Effects of Astaxanthin on Reverse Cholesterol Transport and Atherosclerosis in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Tang-Bin Zou ◽  
Shan-Shan Zhu ◽  
Fei Luo ◽  
Wei-Qiao Li ◽  
Xue-Rong Sun ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
Scavenger Receptor ◽  
Hdl Cholesterol ◽  
High Plasma ◽  
Cholesterol Transport ◽  
Atp Binding ◽  
Type I ◽  
Aortic Sinus ◽  
Atp Binding Cassette Transporter ◽  
Atp Binding Cassette

High plasma level of HDL-cholesterol (HDL-C) has been consistently associated with a decreased risk of atherosclerosis (AS); thus, HDL-C is considered to be an antiatherogenic lipoprotein. The development of novel therapies to enhance the atheroprotective properties of HDL may have the possibility of further reducing the residual AS risk. Reverse cholesterol transport (RCT) is believed to be a primary atheroprotective activity of HDL, which has been shown to promote the efflux of excess cholesterol from macrophage-derived foam cells via ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) and then transport it back to the liver for excretion into bile and eventually into the feces. In the current study, we investigated the effects of astaxanthin on RCT and AS progression in mice. The results showed that short- and long-term supplementation of astaxanthin promote RCT in C57BL/6J and ApoE−/−mice, respectively. Moreover, astaxanthin can relieve the plaque area of the aortic sinus and aortic cholesterol in mice. These findings suggest that astaxanthin is beneficial for boosting RCT and preventing the development of AS.

Scavenger receptor class B type I mediates biliary cholesterol secretion independent of ATP-binding cassette transporter g5/g8 in mice

Hepatology ◽  
2009 ◽  
Vol 50 (4) ◽  
pp. 1263-1272 ◽  
Author(s):  
Harmen Wiersma ◽  
Alberto Gatti ◽  
Niels Nijstad ◽  
Ronald P. J. Oude Elferink ◽  
Folkert Kuipers ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Atp Binding ◽  
Type I ◽  
Biliary Cholesterol ◽  
Atp Binding Cassette Transporter ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Biliary Cholesterol Secretion ◽  
Cholesterol Secretion ◽  
Atp Binding Cassette

scholarly journals E17241 as a Novel ABCA1 (ATP-Binding Cassette Transporter A1) Upregulator Ameliorates Atherosclerosis in Mice

2021 ◽  
Author(s):  
Yanni Xu ◽  
Chang Liu ◽  
Xiaowan Han ◽  
Xiaojian Jia ◽  
Yongzhen Li ◽  
...  
Keyword(s):  
Small Molecule ◽  
Reverse Cholesterol Transport ◽  
Cholesterol Content ◽  
Western Diet ◽  
Liver Cholesterol ◽  
Cholesterol Transport ◽  
Atp Binding ◽  
Macrophage Cells ◽  
Atp Binding Cassette Transporter ◽  
Atp Binding Cassette

Objective: Reverse cholesterol transport, removing excess cholesterol from peripheral tissues, is an important therapeutic target for atherosclerosis treatment. In this study, we propose a new small molecule, E17241, that may be used to treat atherosclerosis by promoting reverse cholesterol transport via ABCA1 (ATP-binding cassette transporter A1) upregulation. Approach and Results: E17241 (4-(1,3-dithiolan-2-yl)-N-(3-hydroxypyridin-2-yl)benzamide) was first identified as an ABCA1 upregulator using a cell-based reporter assay. E17241 significantly increases the mRNA and protein expression levels of ABCA1 in both hepatic cells and macrophages. It promotes cholesterol efflux to apo AI in macrophage cells, and this effect depends on ABCA1. It also decreases total cholesterol content in Ox-LDL (oxidized low-density lipoprotein) loading macrophage cells. E17241 treatment increases the content of 3 H-labeled cholesterol in the feces of male C57BL/6J mice intraperitoneally injected with 3H-cholesterol-labeled macrophage J774 cells, indicating that it could promote in vivo macrophage reverse cholesterol transport. Compared with the western diet group (western diet–fed male ApoE −/− mice), the E17241 group (western diet+E17241 treatment) shows decreased plasma cholesterol, liver cholesterol, and triglyceride levels, with increased fecal cholesterol content. Importantly, E17241 reduces atherosclerotic lesion areas in the en face aorta and aortic sinus while increasing ABCA1 protein levels in both liver and macrophages. Human proteome microarray, coimmunoprecipitation, and other assays demonstrate that PKCζ (protein kinase C zeta) is a binding target of E17241, and this small molecule increases ABCA1 expression in macrophages via the PKCζ-NR (nuclear receptor) pathway. Conclusions: E17241 may be developed as a new lead or drug candidate for the treatment of atherosclerosis by upregulating ABCA1.

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