Protective Effects Of L-Ascorbic Acid On The Cultured Human Umbilical Vein Endothelial Cells Injured By Oxidized Low Density Lipoprotein

Objective To investigate the protective effects of L-ascorbic acid on human umbilical vein endothelial cells (HUVECs) injured by oxidized low density lipoprotein(ox-LDL) and explore its probable mechanism.Methods Confluent cultures of HUVECs were exposed respectively to the different doses of ox-LDL and L-ascorbic acid for 24h. Lactate dehydrogenase(LDH) activity in cell medium and in cell lysate and glutathione(GSH) production in cell lysate were measured, while the endothelial nitric oxide synthase( eNOS) activity and nitric oxide (NO) production induced by acetylcholine were assessed. The correlation between eNOS activity and NO production was analyzed.Results ox-LDL inhibited markedly eNOS activity and NO production in dose- dependent manner. The positive correlation between eNOS activity and NO production was significant (ri=0.8480,p<0.05) (2) These effects induced by ox-LDL were attenuated after the administration of the different doses (lOOumol/L, 300umol/L) of L-ascorbic acid. Moreover, the positive correlation between eNOS activity and NO production was significant (r2=0.9844, p<0.01;r3=0.8802, p<0.05). ox-LDL increased LDH activity and cell mortality in cell medium(P<0.01) and L-ascorbic acid inhibited the effect.L-ascorbic acid did not affect the production of GSH in cell lysate.Conclusions Ox-LDL might injury endothelial cells directly via LOX-1 receptor. (2) The decrease of eNOS activity induced by ox-LDL resulted in the reduction of NO production. L-ascorbic acid could protect HUVECs injured by ox-LDL. These effects were associated with not only its extracellular antioxidationbut also an increase of bioavailability and affinity of tetrahydrobiopterin. These data indicate that the protective role of L-ascorbic acid may retard the pathogenesis of atherosclerosis.