Amorphous nano-selenium quantum dots improve endothelial dysfunction in rats and prevent atherosclerosis in mice through Na/H exchanger 1 inhibition.

Authors:
Ge Wang
Ge Wang
School of Biomedical Engineering and Sciences
United States
He Wang
He Wang
West China Second University Hospital
Chengdu Shi | China
Yu-ming Guo
Yu-ming Guo
School of Public Health
Ping Song
Ping Song
Center for Molecular and Translational Medicine
Atlanta | United States
Jian Xu
Jian Xu
College of Chemistry
Berkeley | United States
Peng Li
Peng Li
State Key Laboratory of Quality Research in Chinese Medicine
China
Shuangxi Wang
Shuangxi Wang
University of Oklahoma Health Sciences Center
United States

Vascul Pharmacol 2019 Apr 26;115:26-32. Epub 2019 Jan 26.

Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan, China. Electronic address:

Aim: Selenium, a trace element involved in important enzymatic activities inside the body, has protective effects against cardiovascular diseases including atherosclerosis. The safe dose of selenium in the organism is very narrow, limiting the supplementation of selenium in diet. The aim of this study is to explore whether selenium quantum dots (SeQDs) prevent atherosclerosis and to investigate the potential mechanisms.

Methods: An amorphous form of SeQDs (A-SeQDs) and a crystalline form of SeQDs (C-SeQDs) were prepared through self-redox decomposition of selenosulfate precursor. Endothelial dysfunction was induced by balloon injury plus high fat diet (HFD) in rats. Atherosclerotic model was established by feeding Apoe mice with HFD.

Results: Administrations of A-SeQDs but not C-SeQDs dramatically improved endothelium-dependent relaxation, and accelerated would healing in primary endothelial cells isolated from rats, which was comprised by co-treatment of LiCl. Lentivirus-mediated knockdown of Na/H exchanger 1 (NHE1) abolished LiCl-induced endothelial dysfunction in rats. In cultured endothelial cells, A-SeQDs, as well as cariporide, inhibited NHE1 activities, decreased intracellular pH value and Ca concentration, and reduced calpain activity increased by ox-LDL. These protective effects of A-SeQDs were reversed by LiCl treatment in endothelial cells. In Apoe mice feeding with HFD, A-SeQDs prevented endothelial dysfunction and reduced the size of atherosclerotic plaque in aortic arteries. Further, lentivirus-mediated NHE1 gene overexpression abolished the protective effects of A-SeQDs against endothelial dysfunction and atherosclerosis in Apoe mice.

Conclusion: A-SeQDs prevents endothelial dysfunction and the growth of atherosclerotic plaque through NHE1 inhibition and subsequent inactivation of Ca/calpain signaling. Clinically, the administration of A-SeQDs is an effective approach to treat atherosclerosis.

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Source
http://dx.doi.org/10.1016/j.vph.2019.01.005DOI Listing
April 2019
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