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Am J Physiol Endocrinol Metab (August 13, 2002). doi:10.1152/ajpendo.00198.2002
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Articles in PresS, published online ahead of print August 13, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00198.2002
Submitted on May 8, 2002
Accepted on July 31, 2002

E-selectin inducing activity in plasma from type 2 diabetic patients with maculopathy

Soren T Knudsen1*, Catherine H Foss1, Per L Poulsen1, Toke Bek2, Thomas Ledet3, Carl E Mogensen1, and Lars M Rasmussen3

1 Medical Department M (Diabetes & Endocrinology), Aarhus University Hospital, Aarhus, Denmark
2 Eye Department, Aarhus University Hospital, Aarhus, Denmark
3 Research Laboratory for Biochemical Pathology, Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark

* To whom correspondence should be addressed. E-mail: stk{at}dadlnet.dk.

Diabetic maculopathy (DMa) is the most prevalent sight-threatening type of retinopathy in type 2 diabetes and a leading cause of visual loss in the western world. Activation of endothelial cells with enhanced expression of leucocyte-adhesion molecules may contribute to the development of DMa. In the present study we examined whether plasma from type 2 diabetic patients with DMa contains factor(s) capable of inducing expression of the adhesion molecules E-selectin and VCAM-1 in cultured endothelial cells. In addition, the effect on cellular proliferation was estimated. Four gender-, age-, and duration (diabetes groups) matched groups of each twenty subjects participated: a) subjects with normal glucose tolerance (NGT), b) subjects with impaired glucose tolerance (IGT), c) type 2 diabetic patients without retinopathy, and d) type 2 diabetic patients with DMa. Fasting plasma was added to in vitro grown human umbilical vein endothelial cells for 6 hours, after which E-selectin and VCAM-1 expression were measured. Proliferation was evaluated by thymidine incorporation. The individuals were characterized by measurement of 24 hour ambulatory blood pressure, urinary albumin excretion rate, HbA1c, and blood lipids. In patients with diabetes, we performed fundus photography and flourescein angiography. Plasma from type 2 diabetic patients with DMa induced a significantly higher expression of E-selectin in endothelial cells than did plasma from subjects with NGT (259 ±23 x 103 vs. 198 ± 19 x 103 arb. absorbance units; p < 0.05). There were no significant differences in plasma stimulatory effects on VCAM-1 expression or on thymidin incorporation between groups. No significant correlations were observed between the expression of E-selectin and HbA1c or fasting blood glucose. These findings suggest that plasma from type 2 diabetic patients with maculopathy contains factor(s) capable of inducing the expression of E-selectin in endothelial cells. Enhanced expression of E-selectin may contribute to the development of maculopathy in type 2 diabetes.






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