title: Alpha-linolenic acid exerts an endothelial protective effect against high glucose injury via PI3K/Akt pathway.
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.
authors.affiliation: Department of Cardiology, Tangdu hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Wenqing
authors.initials: W
authors.lastname: Wang
authors.forename: Ru
authors.initials: R
authors.lastname: Tie
authors.forename: Fei
authors.initials: F
authors.lastname: Tian
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Liang
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Xing
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Xi
authors.forename: Siwang
authors.initials: S
authors.lastname: Wang
authors.forename: Qiangsun
authors.initials: Q
authors.lastname: Zheng
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D001786:Blood Glucose; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000097:blood / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D017962:alpha-Linolenic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D007328:Insulin; D020011:Protective Agents; D017962:alpha-Linolenic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt