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Abstract
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- f ), 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- f 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- f 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.