oa Role of Oxidative Stress in Hyperglycemia Induced Endoplasmic Reticulum Stress Associated Vascular Dysfunction

Background: The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications has been correlated to the hyperglycemia induced oxidative stress (OS) and associated endothelial dysfunction (ED). Additionally, the Endoplasmic Reticulum (ER) stress response, otherwise known as the Unfolded Protein Response (UPR), has been implicated in hyperglycemia associated ED. However, the role of OS in hyperglycemia induced ER stress associated ED remains unclear.

Objective: The present study evaluated the role of OS in hyperglycemia induced ER stress associated ED and whether antioxidant treatment could aid in the reversal the adverse effects hyperglycemia induced ER stress and ED.

Methods: Endothelial cells (ECs) were exposed to normal (NG) and high glucose (HG) for 24 and 48hrs in the presence and absence of the anti-oxidant N-acetyl cysteine (NAC). The level of oxidative stress in the cells was analyzed by DCFDA fluorescence staining levels of ER stress proteins GRP78, PERK and IRE1 were analyzed by immunoblotting.

Results: DCFDA staining indicated that OS significantly increased in HG exposed ECs while this effect was reversed upon in NAC treated endothelial cells. ER stress was significantly increased in HG treated cells as indicated by the changes in the level of ER stress proteins.

Conclusion: The data suggests that hyperglycemia induced OS plays a major role in ER stress and associated ED. Amelioration of OS by suitable antioxidant treatment may be used as therapeutic target for the treatment of diabetes associated cardiovascular diseases. However, more studies are warranted on the choice and dosage the of anti-oxidant, time of administration and supplementation of the anti-oxidant, duration of therapy and choice of treatment subjects to further evaluate the efficacy of anti-oxidant therapy in the treatment of cardiovascular conditions associated with diabetes.