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Selenium Inhibits Homocysteine-Induced Endothelial Dysfunction and Apoptosis via Activation of AKT
Hui Ren1, Jianjun Mu, Jingjing Ma
1Department of Cardiology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Insights
Selenium protects against homocysteine-induced endothelial dysfunction by reducing apoptosis and improving cell function via the AKT pathway. This offers potential therapeutic strategies for cardiovascular diseases (CVD).
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Function
- Nutritional Biochemistry
Background:
- Endothelial cell dysfunction is a key factor in cardiovascular diseases (CVD).
- Elevated plasma homocysteine (Hcy) is linked to CVD, while selenium shows protective effects.
- The precise mechanisms of selenium's action against Hcy-induced endothelial dysfunction were previously unclear.
Purpose of the Study:
- To investigate the protective effects of selenium against homocysteine-induced endothelial dysfunction.
- To elucidate the molecular mechanisms underlying selenium's action, particularly involving the AKT pathway.
Main Methods:
- An animal model of homocysteine-induced endothelial dysfunction was established.
- Assessed endothelial cell viability, migration, and apoptosis (Caspase-3, Bax, Bcl-2).
- Measured nitric oxide (NO) levels and endothelial nitric oxide synthetase (eNOS) expression and phosphorylation, investigating the role of the AKT pathway.
Main Results:
- Selenium administration prevented endothelial injury and improved endothelium-dependent relaxation in the presence of homocysteine.
- Selenium dose-dependently reversed impaired endothelial cell viability and migration, and inhibited apoptosis.
- Selenium promoted NO release by upregulating eNOS expression and phosphorylation, mediated through the AKT pathway.
Conclusions:
- Selenium protects endothelial cells from homocysteine-induced damage and apoptosis via the AKT signaling pathway.
- These findings suggest selenium as a potential therapeutic agent for preventing or treating CVD associated with hyperhomocysteinemia.
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.
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