Increased expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured endothelial cells exposed to serum from type 1 diabetic patients: no effects of high glucose concentrations.
Activation of the arterial endothelium may play an important role in the development of an atherosclerosis-prone vascular wall in diabetes. The induction of the adhesion molecules VCAM-1 and E-selectin on activated endothelial cells is crucial in monocyte recruitment during the atherogenic process. In the present study, we investigated whether sera from type 1 diabetic patients and non-diabetic persons are capable of inducing expression of VCAM-1 and E-selectin in human endothelial cells cultured in vitro. First, it was found that the addition of serum from non-diabetics to the cultures resulted in expression of adhesion molecules above basal level and also increased the cellular response to the cytokine tumor necrosis factor-alpha (TNF-alpha), a strong inducer of both adhesion molecules. Moreover, it was found that, on average, sera from 17 diabetic males induced a higher expression of VCAM-1 in the endothelial cells after 6 h of incubation than samples from 20 non-diabetic age-matched males (p < 0.05). No difference between the diabetic and non-diabetic group was seen in the expression of E-selectin. Likewise, no differences were observed between the effects of the sera to induce TNF-alpha responsivity. A series of experiments showed that alterations in the glucose concentrations of the growth medium (5.5-13.5 mmol/L) did not change the cellular content of either VCAM-1 or E-selectin before and after TNF-alpha treatment. In conclusion, it has been shown that sera from diabetic patients contain component(s), capable of inducing VCAM-1 expression in endothelial cells independent of hyperglycemia. Augmented induction of endothelial VCAM-1 expression by circulating factor(s) may play a role in the development of atherosclerosis in diabetes.
Rasmussen
L M
LM
Laboratory for Molecular Pathology, Institute of Pathology, University Hospital of Aarhus, Kommunehospitalet, Aarhus, Denmark. lmras@dadlnet.dk
Schmitz
O
O
Ledet
T
T
D001769:Blood; D001786:Blood Glucose; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D001786:Blood Glucose; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1