Endothelial cell dysfunction secondary to the adhesion of diabetic erythrocytes. Modulation by iloprost.
We previously showed the correlation between the extent of vascular complications and erythrocyte adherence to endothelium in diabetes mellitus. The accumulation of advanced glycation end products (AGEs) on the erythrocyte surface in diabetes mediates their interaction with endothelial cells through a specific endothelial receptor for AGEs (RAGE). Binding of diabetic erythrocytes to endothelial cells resulted in evidence of oxidant stress responsible for a range of cellular perturbations. In the present study, we have investigated the effect of iloprost, a prostacyclin analog, on several activities modified by diabetic erythrocyte-endothelium interaction: 1) generation of oxidant stress based on production of thiobarbituric acid reactive substances (TBARS: control: 2.37 +/- 0.32 versus iloprost: 1.39 +/- 0.005 mumol/10(11) cells), 2) alteration of the endothelial barrier function as measured by an increase permeability to 125I-albumin (control: 13.31 +/- 0.85 versus iloprost: 9.45 +/- 0.7 10(-7) cm/s) of the endothelial cell monolayer, 3) modification of the endothelial cell function showed by an increase in interleukin-6 release (control: 21.66 +/- 3.11 versus iloprost 15.45 +/- 0.76 ng/10(6) cells). The increase in permeability to albumin as well ass TBARS production and interleukin-6 release were inhibited by iloprost (10(-8)-10(-6) mol/l) treatment in a dose-dependent fashion. These results indicate that erythrocyte associated AGEs might alter endothelial cell function. The perturbations can be limited in vitro by iloprost.
Zoukourian
C
C
Laboratoire de Biologie Vasculaire et Cellulaire, Paris, France.
Wautier
M P
MP
Chappey
O
O
Dosquet
C
C
Rohban
T
T
Schmidt
A M
AM
Stern
D
D
Wautier
J L
JL
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004730:Endothelium, Vascular / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology*; D005260:Female; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D016285:Iloprost