Objective Neutrophil-endothelial adhesion is crucial to vascular injury, the major cause of diabetic vascular complications. We studied the mechanism of cardio-protective effect of Alpha-linolenic acid (ALA).
Methods Human umbilical vein endothelial cells (HUVECs) were cultured in 5.5 mmol/l and 33 mmol/l for 72 h. ALA with different concentrations was (were) added with defatted bovine serum albumin as a carrier for 18 h before(del) incubation with high glucose. The effects of ALA on high glucose-induced activation of endothelial cells were then examined.
Results ALA (10 to 100 μmol/l) decreased the adhesion of human neutrophilic polymorphonuclear leukocytes (PMN) to HUVECs stimulated with high glucose (33 mmol/l) for 48 h. However, with a higher concentration, ALA (200 μmol/l) exerted an opposite effect. ALA (50 μmol/l) also inhibited intercellular adhesion molecule-1(ICAM-1) and P-selectin expressions in HUVECs induced by high glucose. ALA enrichment partially prevented the reduction of Akt phosphorylation caused by high glucose. The inhibitory effects of ALA (50 μmol/l) on high glucose–mediated PMN adherence and endothelial adhesion molecule expression were partially abrogated by pretreatment with the PI3K inhibitor LY294002 and wortmannin, suggesting that Akt activation might inhibit activation of endothelial cell induced by high glucose.
Conclusions We conclude that(del) ALA, with a low concentration, acts directly on endothelial cell to inhibit expression of adhesion molecules and neutrophil adhesion mediated by high glucose via a PI3K/Akt-dependent pathway.
- Alphalinonenic acid
- High glucose-mediated endothelial neutrophil adhesion inhibition
- Adhesion molecule expression
- PI3KAkt pathway