Participation of high glucose concentrations in neutrophil adhesion and surface expression of adhesion molecules on cultured human endothelial cells: Effect of antidiabetic medicines

• Published in: Journal of diabetes and its complications Vol. 16; no. 3; pp. 201 - 208
• Main Authors: Omi, Hitoshi, Okayama, Naotsuka, Shimizu, Manabu, Okouchi, Masahiro, Ito, Shigenori, Fukutomi, Tatsuya, Itoh, Makoto
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2002; Elsevier Science
• Subjects: Aldose reductase inhibitor; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Carbazoles - pharmacology; Cardiology. Vascular system; Cell Adhesion - physiology; Cells, Cultured; E-selectin; E-Selectin - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Enzyme Inhibitors - pharmacology; Glucose - pharmacology; Heart; Humans; Hypoglycemic Agents - pharmacology; Indoles - pharmacology; Intercellular adhesion molecule-1; Intercellular Adhesion Molecule-1 - metabolism; Medical sciences; Myocarditis. Cardiomyopathies; Neutrophils - physiology; P-selectin; P-Selectin - metabolism; Peroxidase - metabolism; Protein Kinase C - antagonists & inhibitors; Sulfonylurea; Umbilical Veins; Aldose reductase inhibitor; E-selectin; Sulfonylurea; P-selectin; Intercellular adhesion molecule-1; Endocrinopathy; Cell culture; Epalrestat; Glimepiride; Participation; Endothelial cell; Cardiovascular disease; Glucose; Myocardial disease; Vascular disease; Molecules; Hyperglycemia; Heart disease; Atherosclerosis; Glibenclamide; Cerebrovascular disease; Human; Nervous system diseases; Stroke; Diabetes mellitus; Inflammation; Concentration; Gene expression; Enzyme immunoassay; Adhesion; Cerebral disorder; Medicine; Central nervous system disease; Gliclazide; Neutrophil; Troglitazone
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/S1056-8727(01)00163-5

Background: Atherosclerosis and vascular inflammation induced by hyperglycemia are important factors in the promotion of diabetic complications. One of the earliest events in the inflammatory process is increased binding of neutrophils to endothelial cells. Since vascular inflammation has been recently reported to be crucial for the onset of atherosclerosis-mediated serious diseases (acute myocardial infarction, stroke), in this study, we examined the effects of high glucose concentrations on endothelial–neutrophil cell adhesion and surface expression of endothelial adhesion molecules. We also evaluated the effects of various antidiabetic medicines on these events. Methods: Human umbilical vein endothelial cells (HUVECs) were first cultured for 48 h in the glucose-rich medium, and neutrophils from healthy volunteers were then added and allowed to adhere for 30 min. Adhered neutrophils were quantified by measuring myeloperoxidase (MPO) activities, and surface expression of endothelial adhesion molecules was determined using an enzyme immunoassay. Results: High glucose concentrations (over 27.8 mM) increased endothelial–neutrophil cell adhesion and expression of endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin). These events were protein kinase C (PKC) dependent, because PKC inhibitors, but not other intracellular second messenger inhibitors, significantly blocked them. Among antidiabetic medicines, a sulfonylurea, gliclazide (but not glibenclamide or glimepiride), and an aldose reductase inhibitor, epalrestat, significantly inhibited these events; however, a new K ATP-channel blocker, netegulinide, a biguanide, metformine, or an insulin sensitizer, troglitazone, did not. Conclusions: Our data is consistent with hyperglycemia-mediated vascular inflammation through increases in neutrophil adhesion and expression of endothelial adhesion molecules. These events might lead to the onset of atherosclerosis-mediated serious diseases, but could be inhibited by something perhaps, such as gliclazide and epalrestat.