High glucose–induced endothelial progenitor cell dysfunction

Abstract

Vascular complications contribute significantly to morbidity and mortality of diabetes mellitus. The primary cause of vascular complications in diabetes mellitus is hyperglycaemia, associated with endothelial dysfunction and impaired neovascularization. Circulating endothelial progenitor cells was shown to play important roles in vascular repair and promoting neovascularization. In this review, we will demonstrate the individual effect of high glucose on endothelial progenitor cells. Endothelial progenitor cells isolated from healthy subjects exposed to high glucose conditions or endothelial progenitor cells isolated from diabetic patients exhibit reduced number of endothelial cell colony forming units, impaired abilities of differentiation, proliferation, adhesion and migration, tubulization, secretion, mobilization and homing, whereas enhanced senescence. Increased production of reactive oxygen species by the mitochondria seems to play a crucial role in high glucose-induced endothelial progenitor cells deficit. Later, we will review the agents that might be used to alleviate dysfunction of endothelial progenitor cells induced by high glucose. The conclusions are that the relationship between hyperglycaemia and endothelial progenitor cells dysfunction is only beginning to be recognized, and future studies should pay more attention to the haemodynamic environment of endothelial progenitor cells and ageing factors to discover novel treatment agents.

Acidic preconditioning of endothelial colony-forming cells (ECFC) promote vasculogenesis under proinflammatory and high glucose conditions in vitro and in vivo

“…On the other hand, although diabetes is considered one of the main target diseases for cell therapy due to the frequent ischemic events and wound healing impairments, studies regarding the effect of high glucose conditions on ECFC survival are scarce and controversial. While some studies described a direct cytotoxic effect [ 19 , 20 ], others are in full agreement with our findings showing that high glucose alone failed to induce apoptosis but inhibited ECFC angiogenic activity [ 12 , 18 , 21 ]. We also found that high glucose potentiated apoptosis triggered by TNFα, an effect that was significantly prevented by acidic preconditioning.…”

“…Although diabetes, especially the type 2 class, is one of the main target diseases for cell therapy due to its well-known healing impairments, studies regarding the effect of high glucose conditions on ECFC survival are scarce and controversial [ 12 ]. Our results revealed that high glucose alone failed to induce ECFC death (Fig.…”

Mechanisms of Diabetes-Induced Endothelial Cell Senescence: Role of Arginase 1

“…In human umbilical vein endothelial cells (HUVECs), HG treatment was found to increase the proportion of cells showing increased levels of SA β-Gal activity [ 37 ]. Endothelial progenitor cells that were isolated from healthy subjects exposed to HG conditions or endothelial progenitor cells that were isolated from diabetic patients were also found to exhibit enhanced senescence [ 38 ]. In the present study, we have shown that A1 induces premature senescence in diabetic retinas.…”

Overexpression of miR‑17‑5p protects against high glucose‑induced endothelial cell injury by targeting E2F1‑mediated suppression of autophagy and promotion of apoptosis

“…Increasing evidence has shown that diabetes mellitus-induced hyperglycemic conditions cause vascular endothelial damage (1,2) demonstrating that hyperglycemia is associated with endothelial dysfunction and reduced blood vessel growth, with angiogenesis often compromised in patients with diabetes. Endothelial dysfunction has long been considered as the first event in the development of atherosclerosis and clinical events (3). Therefore, the maintenance of an intact endothelial layer and improvement of its functions are essential for the maintenance of healthy blood vessels and the prevention of cardiovascular complications associated with diabetes.…”