Selenoprotein S attenuates endothelial dysfunction in a diabetic vascular chip

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Diabetic Complications Research

Background:

• Endothelial dysfunction (ED) initiates diabetic vascular complications, driven by the complex intravascular microenvironment.
• Existing models lack the dynamic simulation needed to study multifactor-induced ED mechanisms.
• Selenoprotein S (SELENOS) was previously linked to protection against oxidative stress-induced endothelial injury.

Purpose of the Study:

• To develop a dynamic microfluidic model of the diabetic vascular endothelial microenvironment.
• To investigate the regulatory signaling pathway of SELENOS in diabetic ED.
• To explore SELENOS as a potential therapeutic target for diabetic macrovascular complications.

Main Methods:

• Development of an integrated microfluidic chip to simulate the diabetic vascular endothelial microenvironment.
• Utilizing human aortic endothelial cells (HAECs) exposed to multifactor-induced oxidative stress.
• Analysis of SELENOS expression and its role in regulating the PKCα/PI3K/Akt/eNOS signaling pathway.

Main Results:

• The microfluidic chip successfully simulated multifactor-induced oxidative stress, showing synergistic effects on HAECs.
• Multifactor-induced oxidative stress upregulated SELENOS expression in HAECs.
• SELENOS protected HAECs by modulating the PKCα/PI3K/Akt/eNOS pathway in the simulated diabetic microenvironment.

Conclusions:

• The developed diabetic vascular chip is a valuable tool for studying vascular endothelial function and ED.
• SELENOS plays a protective role against oxidative stress-induced endothelial injury via the PKCα/PI3K/Akt/eNOS pathway.
• SELENOS represents a potential novel therapeutic target for preventing and treating diabetic macrovascular complications.