Modulation by high glucose of adhesion molecule expression in cultured endothelial cells

Abstract

SummaryWe evaluated the influence of high ambient glucose on cellular expression of adhesion molecules, known to mediate endothelial interaction of leucocytes and monocytes. Paired cultures of individual isolates of human umbilical vein endothelial cells (HUVECs) were studied by fluorescence activated cell sorter analysis after exposure to 30 vs 5 mmol/1 glucose. Incubation of HUVECs for 24h in 30 mmol/1 glucose increased ICAM-1 (intercellular adhesion molecule-i; 116.4 _+ 16.9 % of control, p _< 0.05), but not PECAM (platelet endothelial cell adhesion molecule) expression, compared to cultures kept in 5 mmol/1 glucose. Long-term exposure (13 + 1 days) of HUVECs to 30 mmol/1 glucose increased expression of ICAM-1 to 122.5 ___ 32.2 % (p < 0.002) and reduced that of PECAM to 86.9 __+_ 21.3 % vs the respective control culture in 5 mmol/1 glucose (p < 0.02). Stimulation of confluent HUVECs, kept in 30 vs 5 mmol/1 glucose for 13 + 1 days, with 20 U/ ml interleukin-1 for 24 h (ICAM-1) and 4 h (endothelial leukocyte adhesion molecule 1) resulted in reduced ICAM-1 (84.8 _+ 27.0 %,p < 0.05) and endothelial leukocyte adhesion molecule-1 (87.6 + 22.4 %, p < 0.05) expression vs control cells, while that of PE-CAM (t: 24 h) and vascular cell adhesion molecule-1 (t: 16 h) remained unchanged. In conclusion, it appears that differences in expression of adhesion molecules on HUVECs in response to high glucose reflects endothelial glucose toxicity, which may also induce endothelial dysfunction in diabetes. [Diabetologia (1995[Diabetologia ( ) 38: 1367[Diabetologia ( -1370 Key words High glucose, adhesion molecules, endothelial cells, interleukin-1, diabetes mellitus.Both insulin-dependent and non-insulin-dependent diabetes mellitus are associated with an increased risk for atherosclerosis. Endothelial dysfunction, which precedes the development of atherosclerotic lesions in diabetic patients, includes accelerated dis- appearance of capillary endothelium, weakening of intercellular junctions, altered protein synthesis and the appearance of specific adhesive glycoproteins on endothelial cells [1], promoting local attachment of monocytes and leukocytes as well as their transendothelial migration. The mechanisms leading to elevated plasma levels of shed soluble adhesion molecules in diabetes are unknown and may include their increased synthesis due to disease-specific factors, decreased clearance or just reflect the presence of inflammatory processes. As blood glucose levels, glycated haemoglobin and late diabetes-associated vascular complications are closely correlated [2], this study was designed to evaluate the effect of high ambient glucose concentrations on basal and interleukin-1 (IL-1) stimulated expression of the endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule

Vascular targets of redox signalling in diabetes mellitus

“…3) could reorganise the architecture of the cytoskeleton, modulate Ca 2+ -sensitive/-activated transcription factors and signal cascade enzymes resulting in altered gene expression [136,190,191,192] (for review see [135]). In line with these data in beta cells, in endothelial cells the 54,193,194,195,196,197]. Thereby, the impact of Ca 2+ on gene expression exceeded its role in the nuclear envelope, where Ca 2+ is essential for modulating immediate early genes by modulating the DNA-binding of transcription factors (e. g. cAMP-responsive element binding protein CREB [191,192,198,199,200]).…”

Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration

“…Elevated levels of sE-Selectin not only occur after activation of the endothelium but may also reflect recent endothelial cell damage [18]. Recent studies indicate that both glucose [11,36,37], and advanced glycation end-products may damage endothelium and cause shedding of adhesion molecules [38,39].…”

A new look at the heart in diabetes mellitus: from ailing to failing

“…Expression of endothelial molecules in response to high glucose concentrations could account for endothelial interaction with leucocytes and monocytes [121,122]. In addition, impaired fibrinolytic activity of the endothelium has been suggested [123].…”