Abstract

Vitamin D (VitD) exerts protective effects on the endothelium, which is fundamental for vascular integrity, partly by inhibiting free radical formation. We found that VitD prevents high glucose-induced Thioredoxin Interacting Protein (TXNIP) upregulation. Increased amounts of TXNIP are responsible for the accumulation of reactive oxygen species and, as a consequence, of lipid droplets. This is associated with increased amounts of triglycerides as the result of increased lipogenesis and reduced fatty acid oxidation. Remarkably, VitD rebalances the redox equilibrium, restores normal lipid content, and prevents the accumulation of lipid droplets. Our results highlight TXNIP as one of the targets of VitD in high glucose-cultured endothelial cells and shed some light on the protective effect of VitD on the endothelium.

Highlights

  • Vascular endothelial cells (EC) form a quiescent monolayer that coats the inner lumen of all vessels and retains critical functions that are essential to preserve the integrity of the vasculature and, health [1]

  • When the cells were cultured at the highest D-glucose concentration (30 mM), we observed the significant downregulation of Sirtuin 1 (SIRT1), the most evolutionarily conserved member of the sirtuin family, which exerts beneficial effects on dative stress, we analysed the levels of some of the proteins that are implicated in the control of redox balance

  • Observational data have consistently established low serum concentrations of Vitamin D (VitD) in patients with Type 2 Diabetes Mellitus (T2D). It seems that the duration of diabetes rather than glycemic control is associated with VitD deficiency [26]

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Summary

Introduction

Vascular endothelial cells (EC) form a quiescent monolayer that coats the inner lumen of all vessels and retains critical functions that are essential to preserve the integrity of the vasculature and, health [1]. They act as a metabolic interface between the blood and tissues and ensure optimal nutrient and oxygen delivery to all of the tissues [2]. Glucose is partially utilized for endothelial metabolic needs and is delivered to the surrounding cells and tissues.

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