The miRNA‐208 regulates gene expression of slow myosin heavy chain(MHC)in heart. We investigated the role of miRNA‐208 and its target Thyroid Hormone Receptor Associated Protein 1 (THRAP1) in aerobic training (AT) induced cardiac hypertrophy (CH). Female Wistar Rats(n=21)into 3 groups: sedentary (S), Trained 1(T1): swimming sessions of 60′, 5 days/week (10 weeks). Trained 2(T2): similar to T1 until 8th week, on the 9th week the rats swan twice/day and on the 10th week 3 times/day. Were assessed: heart rate (HR), blood pressure (BP) by direct measurement, VO2max by ergoespirometry, soleus citrate synthase (CS) activity by spectrophotometer, ventricular function and CH by echocardiography (EGC), CH by LV/BW ratio (mg/g) and cardiomyocyte diameter (CD), gene expression of atrial natriuretic factor (ANF), skeletal α‐actin, α‐MHC and β‐MHC and miR‐208 by Real‐time PCR and protein content of α and β‐MHC and THRAP1 by Western Blott. AT decreased HR and increased VO2max (11%/T1 and 15%/T2) and CS (47%/T1 and 105%/T2). LV/BW ratio increased 13%/T1 and 28%/T2 and CD increased 20%/T1 and 30%/T2. Gene expression of skeletal α‐actin decreased 53%/T2. The E/A ratio increased and isovolumetric relaxation time and myocardial performance index decreased. MiR‐208 expression decreased 62%/T2 with a decrease of β‐MHC and an increase of α‐MHC gene expression(β/‐71%,α/+37%) and protein content(β/−45 % α/+72%) in T2. THRAP1 protein increased 40%/T2 compared with S. APT induced physiological CH and improved diastolic function. MiR‐208a and β‐MHC expression decreased and THRAP‐1 increased. The decrease of miR‐208 was opposite to disease and can be a therapeutic strategy in pathological CH.

Support: FAPESP/CAPES/NIH