Endothelial dysfunction (ED) is a critical and initiating factor in the genesis of diabetic vascular complications whose occurrence and development is closely related to the complex intravascular microenvironment. However, currently, there is no dynamic model simulating the diabetic vascular endothelial microenvironment that can be used to investigate the mechanism underlying multifactor-induced ED. Here, we developed an integrated microfluidic chip as a new methodological platform to study vascular ED. Selenoprotein S (SELENOS) was found to be involved in the defense against oxidative stress-induced vascular endothelial injury in our previous studies. However, the regulatory signaling pathway underlying this process has not been described. With this chip, we demonstrated that multifactor-induced oxidative stress injury in human aortic endothelial cells (HAECs) has a synergistic effects and upregulates SELENOS expression. Subsequently, SELENOS was found to protect HAECs against multifactor-induced oxidative stress injury by regulating the PKCα/PI3K/Akt/eNOS pathway in the diabetic vascular endothelial microenvironment. Based on these data, our diabetic vascular chip provides a promising tool for studying vascular endothelial function, and SELENOS may be a novel target for prevention and treatment of diabetic macrovascular complications.
Keywords: Diabetes; Endothelial dysfunction; Microfluidic chip; Oxidative stress; Selenoprotein S.
Copyright © 2020. Published by Elsevier Inc.