Relationship between PMN-endothelium interactions, ROS production and Beclin-1 in type 2 diabetes.

Type 2 diabetes is closely related to oxidative stress and cardiovascular diseases. In this study, we hypothesized that polymorphonuclear leukocytes (PMN)-endothelium interactions and autophagy are associated. We evaluated PMN-endothelial interactions, ROS production and autophagy parameters in 47 type 2 diabetic patients and 57 control subjects. PMNs from type 2 diabetic patients exhibited slower rolling velocity (p < 0.001), higher rolling flux (p < 0.001) and adhesion (p < 0.001) in parallel to higher levels of total (p < 0.05) and mitochondrial ROS (p < 0.05). When the protein expression of autophagy markers was analysed, an increase of Beclin-1 (p < 0.05), LC3I (p < 0.05), LC3II (p < 0.01) and LC3II/LC3I ratio (p < 0.05) was observed. Several correlations between ROS and leukocyte-endothelium parameters were found. Interestingly, in control subjects, an increase of Beclin-1 levels was accompanied by a decrease in the number of rolling (r = 0.561) and adhering PMNs (r = 0.560) and a rise in the velocity of the rolling PMNs (r = 0.593). In contrast, in the type 2 diabetic population, a rise in Beclin-1 levels was related to an increase in the number of rolling (r = 0.437), and adhering PMNs (r = 0.467). These results support the hypothesis that PMN-endothelium interactions, ROS levels and formation of autophagosomes, especially Beclin-1 levels, are enhanced in type 2 diabetes.