Article Text
Abstract
Objectives Mounting evidence has indicated that the cardiovascular protective effects of dietary alpha-linolenic acid (ALA), but whether ALA may exert an endothelial protective effect against high glucose injury and the underlying mechanisms remain largely unknown.
Methods Streptozocin-induced diabetic rats were randomised into vehicle (0.01% alcohol) or ALA (500 μg/kg/d) for 4 weeks. Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (28 mmol/L) stimulation for 48 hours.
Results ALA significantly improved concentration-dependent vasorelaxation to ACh in diabetic aortic segments and inhibited endothelial inflammation as evidenced by decreased soluble P-selectin and intercellular adhesion molecule-1 (ICAM-1) in diabetic rats (n = 6-8, P < 0.05). Furthermore, both P-selectin and ICAM-1 expression were significantly increased in high glucose-induced HUVECs, resulting in enhanced neutrophils adhesion to HUVECs compared with normal glucose group (P < 0.01). Treatment with ALA (50 μmol/L) increased Akt phosphorylation, attenuated P-selectin and ICAM-1 expression and thus inhibited neutrophils adhesion in HUVECs exposed to high glucose, all of which were blocked by the PI3K inhibitors LY294002 and wortmannin (P < 0.05).
Conclusions These data indicated that ALA inhibited endothelial inflammation and improved endothelial function in STZ-induced diabetic rats. The anti-adhesive effect of ALA against high glucose injury may partially be mediated by the PI3K/Akt pathway.