Exercise Training, Antioxidant Supplementation and Endothelial Cell Protection

Abstract

Regular exercise is known to have a beneficial effect on endothelial function and prevention of atherosclerosis however the cellular mechanism/s underlying the protection remains unclear. Apoptosis induced by oxidative stress has been implicated in atherosclerosis and vascular dysfunction and exercise and/or antioxidant supplementation may provide a beneficial role in cellular protection against this process. PURPOSE: To examine the efficacy of antioxidant supplementation (α-lipoic acid and α-tocopherol) and/or endurance training on endothelial cell protection. METHODS: Young male rats were assigned to; 1) sedentary, 2) sedentary and antioxidant supplemented, 3) endurance trained or 4) endurance trained and antioxidant supplemented groups for 14 weeks. Endothelial cells were then isolated from the left ventricle and examined for levels of Bcl-2 protein (a pro-survival protein). RESULTS: Bcl-2 levels were increased following antioxidant supplementation compared to the control diet (96±5 vs 409±124 arbitrary units, p < 0.05) whereas exercise training had no effect (P≥0.05) regardless of diet. In vitro administration of α-lipoic acid and α-tocopherol to cultured rat microvascular endothelial cells did not cause any change in Bcl-2, Bax, HSP70, pERK or cell viability (P≥0.05). However, α-lipoic acid caused a dose-dependent increase in caspase-3 activity; activity following addition of 1 μM α-lipoic acid was significantly higher than the vehicle (0.78±0.10 vs 0.25±0.02 umol/min/ml respectively, p < 0.05) with no subsequent increase in DNA fragmentation (p < 0.05). α-tocopherol had no effect on either caspase-3 activity or cell viability. CONCLUSION: Dietary supplementation with α-lipoic acid and α-tocopherol but not exercise training upregulates cytoprotective proteins in endothelial cells in vivo. These effects are not evident in vitro but the increase in caspase-3 activity at higher concentrations of α-lipoic acid may indicate a need for caution in the use of high doses of this antioxidant.