Insulin administration in the mild hyperglycaemia changes expression of proinflammatory adhesion molecules on human aortic endothelial cells (original) (raw)
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Modulation by high glucose of adhesion molecule expression in cultured endothelial cells
Diabetologia, 1995
We 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) 38: 1367-1370] 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
Croatica Chemica Acta, 2008
Expression of E- and P-selectin, vascular adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 and -2 (ICAM-1, ICAM-2) on the endothelial cells’ surface, as an answer to the pathophysiological stimuli, is considered as a main event in the development of the atherosclerosis. The influence of elevated glucose concentration and metformin treatment on the expression of adhesion molecules (CAMs) on human aortic endothelial cells (HAECs) was investigated. HAECs were cultured in a medium with 5.5, 8, 12 and 16.5 mM glucose concentration with or without metformin addition. Controls were percent of CAMs expressed on the HAEC cultivated with a physiological glucose concentration. Glucose in 12 mM concentration, increased E-selectin (62%), VCAM-1 (4 fold) and ICAM-1 (81%) expression. Metformin administration significantly increased ICAM-1 expression in HAECs cultured with 8 mM glucose and increased CAMs expression in cells cultured with 12 mM glucose. Metformin administration ad...
The Journal of Clinical Endocrinology & Metabolism, 2000
Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis. It serves as a ligand for leukocyte function-associated antigen-1 on leukocytes and is partially responsible for the adhesion of lymphocytes, granulocytes, and monocytes to cytokine-stimulated endothelial cells and the subsequent transendothelial migration. Its expression on endothelial cells is increased in inflammation and atherosclerosis. As it has been suggested that insulin and hyperinsulinemia may have a role in atherogenesis, we have now investigated whether insulin has an effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC were prepared from human aortas by collagenase digestion and were grown in culture. Insulin (100 and 1000 U/mL) caused a decrease in the expression of ICAM-1 (messenger ribonucleic acid and protein) by these cells in a dose
Atherosclerosis, 2007
Acute, short-term hyperglycemia is becoming recognized as an important risk factor for several diseases. In the present study, using human aortic endothelial cells (HAECs), we investigated whether short-term high glucose exposure, either on the scale of hours, could enhance the monocyte adhesion and migration to the subendothelium via increasing expression of adhesion molecules and release of chemotactic factors. HAECs stimulated with 25mM d(+)glucose (HG) for not more than 12h, exhibited rapid up-regulation of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein. Although intercellular adhesion molecule-1 (ICAM-1) is considered as a marker of the activation of the atherogenic process, early up-regulation was not observed, and VCAM-1 and MCP-1 protein enhance was sufficient to increase the adhesiveness of human monocytes U-937 to HAECs and their transmigration into the subendothelial space after 4h HG stimulation; both effects were prevented by interfering with monoclonal antibodies against VCAM-1, CD11b, and MCP-1. An increased intracellular oxidative stress, a translocation of NF-kappaB to the nucleus and a prevention of adhesion and transmigration of U-937 by interfering with NF-kappaB inhibitors was also observed after a short HG treatment. Taken together, these results suggest that either acute hyperglycemic spikes could exert an influence on the onset of diabetic complications and on the development of the atherogenic profile on diabetic and non-diabetic subjects.
Diabetologia, 1999
Although hyperinsulinaemia is an independent risk factor for the development of atherosclerotic lesions [1], mechanisms underlying the atherogenetic actions of insulin are largely unclear. Recent studies have shown that insulin exerts various endothelial effects, such as an increase of endothelin-1 and nitric oxide production [2]. These findings are of particular relevance and suggest insulin might also exert other endothelial effects which, in turn, could trigger and maintain the atherogenetic process. In this context, vascular cell adhesion molecule(VCAM)-1 is an endothelial adhesin whose up regulation is the most important initiating event in atheroma formation [3]. In spite of this, whether or not insulin might influence VCAM-1 expression by the human vascular endothelium is notknown.
Diabetes Care, 1998
OBJECTIVE To evaluate the effects of a 14-day intensive insulin therapy and short-term improvement of glycemic control on serum levels of soluble forms of adhesion molecules, i.e., intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in NIDDM patients with poor glycemic control. RESEARCH DESIGN AND METHODS A total of 16 NIDDM patients were compared with 23 healthy subjects (control group) and investigated before and after intensive insulin treatment. RESULTS On day 0, sE-selectin and sVCAM-1 levels were significantly higher in NIDDM patients than in nondiabetic control subjects (median 87, range 63–115; median 544, range 408–797 vs. 58, 43–80; 443, 395–573 ng/ml, respectively) (P < 0.008 in both cases). On day 15, the fall in sE-selectin levels was significant (P < 0.0001) and at a lesser extent in sVCAM-1 levels (64, 48–85; 506, 417–678 ng/ml, respectively); these levels reached values that no longer differed f...
Relation Between Soluble Adhesion Molecules and Insulin Sensitivity in Type 2 Diabetic Individuals
Diabetes Care, 2001
OBJECTIVE—The purpose of this study was to explore the relation between insulin resistance and plasma levels of soluble adhesion molecules and to examine the effects of acute hyperinsulinemia on these molecules in type 2 diabetic individuals. RESEARCH DESIGN AND METHODS—Intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E- and P-selectin plasma concentrations were measured in 36 nonobese type 2 diabetic patients without cardiovascular disease and in 7 healthy subjects. Insulin sensitivity was assessed by a 4-h euglycemic (∼5 mmol/l)-hyperinsulinemic (∼300 pmol/l) clamp performed in combination with [3H]3-d-glucose infusion. RESULTS—Diabetic subjects were insulin resistant but did not show plasma concentrations of adhesion molecules that were significantly higher than control subjects. In diabetic subjects, plasma ICAM-1 and E-selectin were negatively correlated with total glucose disposal during the insulin clamp (r = −0.432, P < 0.01; and r =...
Journal of International Medical Research
Objective Type 2 diabetes mellitus (T2DM) is a main risk factor for development of cardiovascular diseases (CVDs) and endothelial dysfunction. This study aimed to investigate serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), and endothelium selectin (sE-selectin) in T2DM patients with macrovascular complications. Methods A cross-sectional study of 21 controls, 30 T2DM patients without CVDs, and 30 T2DM patients with CVDs was conducted. Serum levels of soluble adhesion molecules including sVCAM-1, sICAM-1, and sE-selectin were determined using ELISA. Results Serum levels of sVCAM-1, sICAM-1, and sE-selectin were higher in T2DM patients than in controls. Levels of serum sVCAM-1 were higher in T2DM patients with CVDs compared with T2DM patients without CVDs. In T2DM patients with CVDs, significant positive associations were observed between sVCAM-1, sICAM-1, and sE-selectin levels (r = 0.575, p = 0.001 and r = 0.378, p = 0...
Diabetology International, 2018
The experimental aim of this study was to determine, in vitro, the effects of glucose-induced EMPs on endothelial cell expression of E-selectin, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 and platelet cell adhesion molecule-1 (PECAM-1). Human umbilical vein endothelial cells (HUVECs) were cultured (3rd passage) and plated in 6-well plates at a density of 5.0 × 10 5 cells/condition. HUVECs were incubated with media containing either 25 mM d-glucose (concentration representing a hyperglycemic state) or 5 mM d-glucose (normoglycemic condition) for 48 h to generate EMPs. EMP identification (CD144 +) and concentration were determined by flow cytometry. HUVECs (3 × 10 6 cells/condition) were treated with either high glucose-derived EMPs (hgEMPs) or normal glucose-derived (ngEMPs) for 24 h and surface expression of E-selectin (CD62E-PE), ICAM-1 (CD54-FITC), VCAM-1 (CD106-APC) and PECAM-1 (CD31-BV) was assessed by flow cytometry and reported as mean fluorescent intensity (MFI). Hyperglycemic-derived EMPs induced significantly higher surface expression of E
Circulating adhesion molecules levels in type 2 diabetes mellitus and hypertension
International Journal of Cardiology, 2005
Background: Risk factors for atherosclerosis such as hypertension, type 2 diabetes, obesity and dyslipidemia affect endothelial function and stimulate adhesion molecules expression. The aim of the study was to examine endothelial activation in type 2 diabetes and hypertension as indicated by adhesion molecule levels and further to investigate whether the coexistence of the above conditions has a different effect. Methods: Serum levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured in 17 hypertensive type 2 diabetic patients (DM-HY), 32 normotensive type 2 diabetic patients (DM), 11 hypertensive nondiabetic patients (HY) and 15 healthy subjects. Results: In diabetic patients (either DM-HY or DM), soluble E-selectin levels were significantly increased compared to healthy subjects ( p < 0.001). In HY patients, both sE-selectin (66.44 F 71.59 vs. 29.42 F 15.56 ng/ml, p = 0.033) and sVCAM-1 (1529 F 433.33 vs. 1027 F 243.56 ng/ml, p = 0.03) levels were found significantly higher compared to healthy subjects ( p < 0.05). The coexistence of diabetes and hypertension (DM-HY) did not have an additive effect on circulating adhesion molecules levels compared with the levels observed in either diabetes or hypertension. Systolic and diastolic blood pressure (BP) were independent factors correlated respectively with sE-selectin and sVCAM-1 levels (R = 0.454, p = 0.034 and R = 0.578, p = 0.005) in nondiabetic subjects (hypertensive and normotensive). Conclusions: Type 2 diabetes mellitus and hypertension induce endothelial activation as indicated by elevated levels of soluble adhesion molecules. This effect is not different when comorbidity is present. D