Growth hormone influences atrophy pathways in skeletal muscle of heart failure rats (1163.3)

Skeletal muscle atrophy is usually observed in heart failure. Growth hormone (GH) increases muscular mass in several clinical settings. Objective: To evaluate GH administration effects on myogenin, MyoD, MRF4, myostatin, follistatin, PI3K, Akt, atrogin‐1 and MuRF‐1 protein expression, in the gastrocnemius muscle of rats with aortic stenosis‐induced heart failure. Methods: Male Wistar rats were subjected to thoracotomy for ascending aortic stenosis induction. After developing tachypnea, rats were evaluated by echocardiogram and subdivided into three groups (n=8): Sham, aortic stenosis (AS) and AS treated with GH (AS‐GH, 2mg/kg/day for 14 days). At the end of treatment, animals were subjected to echocardiogram and euthanized. Protein expression was analized by Western‐Blot. Statistical analysis: Anova and Tukey. Results: Before treatment, cardiac variables did not differ between AS and AS‐GH groups. GH administration preserved body weight (BW, Sham 492±32; AS 420±32; AS‐GH 486±69 g; p<0.05 AS vs Sham and AS‐GH). Left ventricular posterior wall thickness (Sham 3.22±0.20; AS 3.80±0.36; AS‐GH 4.37±0.67 mm) and right ventricle weight/BW ratio (Sham 0.55±0.03; AS 1.15±0.25; AS‐GH 1.18±0.15 mg/g) were higher in AS and AS‐GH than Sham. MyoD expression was higher in AS group than Sham and unchanged in AS‐GH and Sham (Sham 1.00±1.28; AS 1.71±1.37; AS‐GH 1.21±1.21 arbitrary units). MRF4 levels were higher in AS‐GH than Sham and similar in AS and Sham (Sham 1.00±0.73; AS 1.58±0.42; AS‐GH 3.14±1.61 arbitrary units). Atrogin‐1 was lower decreased in AS‐GH than Sham and AS (Sham 1.00±0.58; AS 1.14±0.87; AS‐GH 0.31±0.16 arbitrary units). Protein expression of myostatin, follistatin, myogenin, PI3K, Akt and MuRF‐1 did not differ between groups. Conclusion: Growth hormone administration modulates myogenic regulatory factors and atrogin‐1 expression in the gastrocnemius muscle of heart failure rats. Grant Funding Source : Supported by Fapesp