Endothelial cell dysfunction in hyperglycemia: Phenotypic change, intracellular signaling modification, ultrastructural alteration, and potential clinical outcomes

Abstract

Hyperglycemia, the hallmark of Diabetes mellitus, is a major risk factor for endothelial dysfunction and vascular complication. In recent years, significant achievements have been made in understanding endothelial cell dysfunction triggered by high glucose concentration. The purpose of this review is to discuss the results of these recent developments. First, the remarkable plasticity of vascular endothelial cell in response to the high glucose insult is emphasized. This is evident through the switch in the cell’s normal quiescent profile into new phenotypes, endowed with biosynthetic, inflammatory, adhesive, proliferative, migratory, pro-atherogenic, and pro-coagulant properties, frequently overlapping each other. Then, we underline the imbalanced expression and activity of transcription and signaling pathways, and the intense metabolic activity that accompanies the change in endothelial cell phenotype. As an adaptation to the high glucose-induced biochemical modification, a severe alteration of cell structure is produced. The review concludes with the clinical outcomes of the subject, emphasizing the high glucose-associated endothelial cell dysfunctional molecules of potential for targeting, and for reducing the impact of hyperglycemia on vascular endothelium. Such interventions may lead to a more efficient therapy for the benefit of those diabetic patients who are at increased cardiovascular risk.