Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 38, Issue 3, Pages 871-882Publisher
KARGER
DOI: 10.1159/000443041
Keywords
Cardiovascular disease; Endothelial cell; Homocysteine; Selenium; Apoptosis
Categories
Funding
- National Science & Technology Pillar Program [2011BAI11B01]
Ask authors/readers for more resources
Background/Aims: Endothelial cells are crucial in vascular homeostasis. Dysfunction of endothelial cells is involved in the development of cardiovascular diseases (CVD). High plasma homocysteine (Hcy) correlates with CVD while selenium supplementation counteracts development of CVD. However, the underlying mechanism remained unclear. Here, we investigated the effects of selenium on homocysteine-induced endothelial dysfunction. Methods: An animal model of Hcy-induced endothelial dysfunction was established by intragastric administration of L-methionine. Plasma NO and von Willebrand factor (vWF) were quantified using NO assay and ELISA kit respectively. Relaxation was measured in thoracic aortic ring assays. Cell viability and migration were detected by Cell Counting Kit-8 and Bio-Coat cell migration chambers respectively. Cellular apoptosis was determined by Annexin V-FITC apoptosis kit. Results: Selenium prevented homocysteine-induced endothelial injury and impairment of endothelium-dependent relaxation. Selenium reversed the impaired viability and migration of endothelial cells induced by homocysteine in a dose-dependent manner. Selenium inhibited the apoptosis of endothelial cells induced by homocysteine, through downregulating of Caspase-3 activity and expression of Caspase-3 and Bax, and by stimulating Bcl-2 expression. Selenium reversed the homocysteine-induced reduction of NO release, and increased the expression and phosphoylation of endothelial nitric oxide synthetase (eNOS) in a dose-dependent manner. Moreover, selenium enhanced AKT phosphorylation, and selenium-induced phosphorylation and expression of eNOS were inhibited by AKT inhibition. NO production, cell viability and migration rescued by selenium were inhibited, while cell apoptosis was reversed by AKT inhibition. Conclusion: Selenium protected against homocysteine-induced dysfunction and apoptosis of endothelial cells through AKT pathway. The observations may provide novel therapeutic opportunities in the treatment of CVD. (C) 2016 The Author(s) Published by S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available