Abstract 16080: Chronic Akt Blockade Aggravates Pathological Hypertrophy and Inhibits Physiological Hypertrophy
Background: Attenuation of adverse myocardial remodeling contributes to improved prognosis after pathological injury of the heart. Activation of Akt in the heart seems to exert positive or negative effects on cardiac function depending on the stimulus which leads to its activation. Here, we investigated the effect of chronic Akt blockade by Deguelin (DEG) on myocardial remodeling and the development of hypertrophy following a pathological stimulus (myocardial infarction and aortic banding) and following exercise training (controlled treadmill running).
Methods: Wistar rats were orally treated with DEG (4.0 mg/kg) for 4 weeks starting one day after induction of myocardial infarction (MI) or aortic banding. Exercise animals received DEG for 4 weeks during the training period.
Results: DEG treatment leads to a significant reduction of phosphorylation of Akt in all groups. 4 weeks after MI, DEG treated animals showed impaired LV function with enhanced LVEDD (12±0,3mm vs 11.1±0,4mm, p<0.05), EDV (439±8μl vs 388± 8μl, p<0.05) and cardiomyocyte size (+20 % vs Veh, p<0.05) compared to vehicle treated animals. Akt inhibition leads to a higher amount of fibrosis in the left ventricle (4.5±0.3% vs 3.3±0.3%, p<0.05). 4 weeks after aortic constriction we observed an augmentation of pathological hypertrophy in the DEG group (increase in cardiomyocyte size more than 20%, p<0.05). Echocardiography revealed increased wall thickness indicating enhanced pathological hypertrophy (AWed: 2.1±0.05mm vs 1.89 ±0.06mm, p<0.05, PWed: 2.08±0.05mm vs 1.87±0.05mm, p<0.01). Development of physiological hypertrophy was completely inhibited by DEG treatment in exercising animals.
Conclusions: Akt blockade aggravates adverse myocardial remodeling and antagonizes physiological hypertrophy.
- © 2010 by American Heart Association, Inc.