Review Article

Old and New Biomarkers Associated with Endothelial Dysfunction in Chronic Hyperglycemia

Table 1

The table summarizes potential epigenetic and metabolomic biomarkers associated with endothelial dysfunction in chronic hyperglycemia.

TechnologyBiomarkers and/or pathwaySource typeReferences

EpigeneticsHMT Set7 overexpression and NF-κB p65 activationHuman aortic endothelial cells (HAECs) exposed to high glucose and aortas of diabetic mice[82]
Hyperacetylation of histone H3K9/K14Human aortic endothelial cells (HAECs) in high glucose or low glucose[57]
SIRT1 overexpressionEndothelial cells (ECs) and tissues from diabetic male C57BL/6 mice[85, 86]
Angiogenesis-associated miRNAs (angioMiRs), inflammation-associated miRNAs (inflammaMiRs), and senescence-associated miRNAs (seneMiRs)Endothelial cells (ECs); human dermal microvascular endothelial cells (HMVECs); human umbilical vein endothelial cells (HUVECs); vascular smooth muscle cells (VSMCs)[58, 87]
miR-155Endothelial cells (ECs); vascular smooth muscle cells (VSMCs); female Apoe–/– mice[88, 89]
miR-126Plasma of sepsis patients and healthy controls; RAW264.7 macrophages; human umbilical vein endothelial cells (HUVECs); human promyelocytic cell line HL-60; endothelial cells derived from mouse embryonic stem (ES) cells; knockdown of miR-126 in zebrafish[9092]
miR-146aHuman umbilical vein endothelial cells (HUVECs)[93]
miR-200cEndothelial cells (ECs); human umbilical vein endothelial cells (HUVECs); C2C12 myoblasts; primary normal human fibroblasts[94, 95]
IncRNAsHuman umbilical vein endothelial cells (HUVECs) cultured under high or normal glucose conditions[97]
IncRNA-MEG3Retinas of STZ-induced diabetic mice; endothelial cells (ECs)[98]

MetabolomicsLow plasma histidine, high butenoylcarnitine
Low hexose, glutamine, and tyrosine
Urine and plasma of T2D patients[109]
Alterations of carbonyl stress, carbohydrate metabolism, amino acid metabolism pathways, in particular vitamin B6, propanoate, and butanoate metabolismMouse aortic cells[110]
Alanine, proline, glycine, serine, and glutamine alterationsHuman aortic endothelial cells (HAECs) exposed to acute and chronic hyperglycemia[111]
Glycosphingolipid pathwayPlasma of hyperglycemic mice and glucosamine-supplemented mice[112]
Gamma-glutamyl cycle impairment and increased methylglyoxalHuman umbilical vein endothelial cells (HUVECs)[114]