Tissue Specific Susceptibility To Vascular Inflammation In Diabetes Based On ICAM-1 As The Inflammatory Marker

Objective: The frequency of diabetes is increasing rapidly worldwide even in developing countries. New evidence indicates that diabetes is pro-inflammatory disease. A central feature of inflammation is the ingress of circulating leukocytes across the endothelium and underlying basement membranes into affected tissue. Inflammatory processes contribute to development of early stages of diabetic retinopathy and macrovascular disease, but the significance of inflammation in other complications is less clear. We investigated the effect of diabetes on vascular ICAM-1 throughout the body.Research Design and Methods: The distribution and expression of ICAM-1 in retina were assessed using immunochemical techniques. ICAM-1 mediated leukostasis was measured by FITC-Con A staining after the heart perfusion. TUNEL Assay was used to evalute the correlation of ICAM-1 expression and endothelium injury and apoptosis. Endothelial ICAM-1 was assessed by conjugating anti-ICAM-1 to fluorescent microspheres, injecting them intravenously into nondiabetic or diabetic rats (8 weeks or 18 weeks of diabetes), and counting the number of microspheres retained in the tissues. Some diabetics were treated with aminoguanidine or sodium salicylate (both known to inhibit early diabetic retinopathy in animals).Results: Immunochemistry revealed that diabetes increased ICAM-1 expression in the whole retina and the immunoreactivity in retinal vasculature that induced the leukostasis in retinal vasculature, and this process resulted in the endothelium injury and apoptosis. ICAM-1 plays a very important role in the development of diabetic retinopathy and could be used as the inflammation marker to assess the tissue specific susceptibility to vascular inflammation in diabetes. There was considerable variability among tissues with regard to diabetes-induced vascular inflammation. Diabetes increased ICAM-1-mediated adherence of microspheres almost 8-fold on retinal vessels, and almost 19-fold in aorta.. In both tissues, either aminoguanidine or salicylate significantly inhibited this increase. Heart and adipose tissue tended to show increased binding in diabetes, but other tissues demonstrated less or no diabetes-induced vascular inflammation. The induction of vascular inflammation especially in retina and aorta in diabetes was similar to that induced by LPS in nondiabetic animals.Conclusions: ICAM-1 induced the endothelium injury and apoptosis that is a very important role in the development of diabetic retinopathy. Diabetes causes a vascular inflammation that affects especially retina and aorta. Inhibition of vascular inflammation offers a therapeutic target to inhibit development of these important complications of diabetes.