Acetylcysteine Prevents Maximal Exercise-Induced Increase In Circulating Mir-126 Expression And Angiogenic Mediators In Intermittent Claudication Patients

In intermittent claudication (IC) patients, maximal exercise increases systemic levels of pro‐angiogenic mediators. The mechanisms responsible for this response are unknown, but oxidative stress may play a role. This study investigated the effects of maximal exercise and antioxidant treatment with N‐acetylcysteine (NAC)on the expression of miR‐126 (an endothelial‐specific microRNA that regulates angiogenesis) and its targets in IC patients. Following a double‐blinded randomized crossover design, 10 patients received oral NAC (1800 mg/day for 4 days plus 2700 mg prior to experimental session) and placebo (PL) before undergoing a treadmill exercise test to maximal leg pain. Blood samples were taken at rest, 1 hour after the ingestion of the last dose, and 30 min after the exercise test. Whole blood miR‐126, PI3KR2, VEGF and eNOS expression were determined by real‐time PCR. Treatment with NAC did not alter baseline expression of miR‐126 and its downstream targets. After maximal exercise, the expression miR‐126 (Fold change PL 1.79 vs NAC 0.79), eNOS (Fold change PL 1.73 vs NAC 1.14) and VEGF (Fold change PL 1.45 vs NAC 0.71) increased relative to baseline (p<0.05), and this response was blunted after NAC. Similarly, PI3KR2 decreased significantly (p<0.05) after exercise with placebo while no change was observed with NAC (Fold change PL 0.56 vs NAC 1.08).In conclusion, oral treatment with NAC prevents maximal exercise‐induced increase in circulating miR‐126 expression and other angiogenic mediators in IC patients. Funding: FAPESP 2013/05883‐8