Endothelial cells' biophysical, biochemical, and chromosomal aberrancies in high‐glucose condition within the diabetic range

Abstract

To date, many studies have been conducted to find out the underlying mechanisms of hyperglycemia-induced complications in diabetes mellitus, attributed to the cellular pathologies of different cells-especially endothelial cells. However, there are still many ambiguities and unresolved issues to be clarified. Here, we investigated the alteration in biophysical and biochemical properties in human umbilical vein endothelial cells exposed to a high-glucose concentration (30mM), comparable to glucose content in type 2 diabetes mellitus, over a course of 120 hours. In addition to a reduction in the rate of cell viability and induction of oxidative stress orchestrated by the high-glucose condition, the dynamic of the fatty acid profile-including polyunsaturated, monounsaturated, and saturated fatty acids-was also altered in favor of saturated fatty acids. Genetic imbalances were also detected at chromosomal level in the cells exposed to the abnormal concentration of glucose after 120 hours. Moreover, the number of tip cells (CD31 /CD34 ) and in vitro tubulogenesis capability negatively diminished in comparison to parallel control groups. We found that diabetic hyperglycemia was associated with a decrease in the cell-cell tight junction and upregulation in vascular endothelial cadherin and zonula occludens (ZO)-1 molecules after 72 and 120 hours of exposure to the abnormal glucose concentration, which resulted in a profound reduction in transendothelial electrical resistance. The surface plasmon resonance analysis of the human umbilical vein endothelial cells immobilized on gold-coated sensor chips confirmed the loosening of the cell to cell intercellular junction as well as stable attachment of each cell to the basal surface. Our findings highlighted the disturbing effects of a diabetic hyperglycemia on either biochemical or biophysical properties of endothelial cells.

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

“…Evidence shows that glucose induces chromosome damage 41 , 42 . Thus, we first asked whether the high glucose content present in InR, Chico and Akt depleted individuals and also in HSD fed larvae affected DNA integrity.…”

Angiopoietin-1 Promotes the Integrity of Neovascularization in the Subcutaneous Matrigel of Type 1 Diabetic Rats

“…There are research findings that diabetic hyperglycemia was associated with a decrease in the cell‐cell tight junction and downregulation of VE-cadherin, ZO-1, and occludin protein expression exposure to the abnormal glucose concentration [45, 46]. The reason for this finding could be that disrupted calcium dependence of EC‐EC connections via VE‐cadherin, morphological rearrangement, and paracellular gap formation was induced after exposure to high glucose [47]. Meanwhile, our data also indicate that exogenous administration of Ang-1 can upregulate expression of junction proteins ZO-1, occludin, and VE-cadherin in the Matrigel of diabetic rat.…”

Alginate‐gelatin encapsulation of human endothelial cells promoted angiogenesis in in vivo and in vitro milieu

“…Angiogenesis or neovascularization is a vital sophisticated procedure of blood vessel formation by engaging endothelial cells (ECs) from vasculature bed (Carmeliet, ). Angiogenesis is touted as a critical phenomenon required for tissue regeneration and successful graft implantation (Rezabakhsh et al, ). The potent role of various factors and signaling pathways have been found in association with the pro‐angiogenic behavior of ECs such as vascular endothelial growth factor (VEGF) and Tyrosine kinase receptors such as VEGFR‐1, 2, Tie‐1 and Tie‐2 (Marti & Risau, ; Nicosia, Nicosia, & Smith, ).…”