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

Abstract：

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 Ca2+ 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 Ca2+/calpain signaling. Clinically, the administration of A-SeQDs is an effective approach to treat atherosclerosis.

journal_name

Vascul Pharmacol

journal_title

Vascular pharmacology

authors

Zhu ML,Wang G,Wang H,Guo YM,Song P,Xu J,Li P,Wang S,Yang L

doi

10.1016/j.vph.2019.01.005

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

26-32

eissn

1537-1891

issn

1879-3649

pii

S1537-1891(18)30362-8

journal_volume

115

pub_type

杂志文章

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