High glucose induces enhanced monocyte adhesion to valvular endothelial cells via a mechanism involving ICAM-1, VCAM-1 and CD18

Upon induction of experimental hyperglycemia (i.e. diabetes) pathological m odifications are early detected (similar to 7 days) at the level of the car diac valves leading rapidly to the development of valvular atheroma. Monocy te adhesion to the Vascular endothelium is one of the initial event at the onset of atherosclerosis. We questioned whether high glucose enhances monoc yte adhesion to the valvular endothelial cells (VEC) so as to explain, in p art, the accelerated atheroma formation that occur in diabetic conditions. To this purpose we compared the adhesion of monocytes to VEC cultured in 5. 5 mM (normal) glucose (NG) or in 33mM (high) glucose (HG) or in high mannit ol (HM) (27.5 mM mannitol plus 5.5 mM glucose), a concentration known to si mulate the hyperosmolar effect of high glucose. After incubation for 30 min at 37 degrees C, the adhesion of monocyte cell line (U937 cells) to VEC wa s quantitated by a fluorimetric assay or by direct counting. Statistical da ta showed a significant increased adhesion of monocytes to VEC grown in HG (up to 4 fold) or in HM (up to 2.7) when compared to normal conditions. Usi ng a battery of specific monoclonal antibodies molecules it was found that the increased adhesion of monocytes to VEC grown in high glucose was specif ically inhibited (p < 0.05) by anti-ICAM-1, anti-VCAM-1 and anti-CD18 monoc lonal antibodies. Together, the results indicate that high glucose induces enhanced monocyte adhesion to VEC via a mechanism involving in part an osmo tic effect and mainly the cell adhesion molecules: ICAM-1, VCAM-1 and CD18.