Abstract
Mounting evidence has indicated that the cardiovascular protective effects of dietary alpha-linolenic acid (ALA), but whether ALA exerts an endothelial protective effect against high glucose injury and the underlying mechanisms remain largely unknown. Streptozocin-induced diabetic rats were randomized treated orally for 4 weeks with vehicle (0.01% alcohol) or ALA (500 µg/kg per day by gavage). Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (28 mmol/L) stimulation for 48 hours. 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. Furthermore, both P-selectin and ICAM-1 expression were increased significantly in high glucose-induced HUVECs, resulting in enhanced neutrophils adhesion to HUVECs compared with normal glucose group. Treatment with ALA (50 µmol/L) increased Akt phosphorylation, attenuated P-selectin and ICAM-1 expressions and thus inhibited neutrophils adhesion in HUVECs exposed to high glucose, all of which was blocked by the PI3K inhibitors LY294002 and wortmannin. These data indicates that ALA inhibits 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.
Highlights
Cardiovascular disease is one of the leading causes of death in the western world and diabetes mellitus has been identified as a primary risk factor [1]
Treatment of diabetic rats with 500 mg/kg alpha-linolenic acid (ALA) did not have any significant effect on blood glucose (26.561.8 mmol/L) and plasma insulin (9.660.2 mU/mL) concentrations compared with vehicle-treated group
We further investigated the effects of ALA on the surface expression (Figure 4A) of P-selectin and intercellular adhesion molecule-1 (ICAM-1) and their protein expression (Figure 4B) in Human umbilical vein endothelial cells (HUVECs) stimulated by high glucose
Summary
Cardiovascular disease is one of the leading causes of death in the western world and diabetes mellitus has been identified as a primary risk factor [1]. Endothelial inflammation and dysfunction play important roles in the pathogenesis of diabetic vascular complications [2,3]. One of the key initial events in that pathological process is the adhesion of neutrophils to endothelial cells which is largely mediated by cellular adhesion molecules (CAMs), such as intercellular adhesion molecule-1 (ICAM-1), Pselectin and E-selectin. Elevated plasma levels of endothelial cell adhesion molecules have been documented in diabetic patients [4,5]. It is, thought that prevention of high glucose-mediated endothelial CAMs expression and restoration of endothelial function may have important implications for pharmacological attempts to prevent the development of vascular diseases occurring in diabetes
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