Effects of growth hormone on cardiac remodeling and soleus muscle in rats with aortic stenosis-induced heart failure

// Aline R.R. Lima 1, * , Luana U. Pagan 1, * , Ricardo L. Damatto 1, * , Marcelo D.M. Cezar 1, * , Camila Bonomo 1, * , Mariana J. Gomes 1, * , Paula F. Martinez 2, * , Daniele M. Guizoni 1, * , Dijon H.S. Campos 1, * , Felipe C. Damatto 1, * , Katashi Okoshi 1, * and Marina P. Okoshi 1, * 1 Botucatu Medical School, Internal Medicine Departament, Sao Paulo State University, UNESP, Botucatu, Brazil 2 School of Physical Therapy, Federal University of Mato Grosso do Sul, Campo Grande, Brazil * These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation Correspondence to: Marina P. Okoshi, email: mpoliti@fmb.unesp.br Keywords: heart failure, skeletal muscle, growth hormone, muscle trophicity, satellite cells Received: March 28, 2017     Accepted: July 29, 2017     Published: August 24, 2017 ABSTRACT Background: Skeletal muscle wasting is often observed in heart failure (HF). The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis is impaired in HF. In this study, we evaluated the effects of GH on soleus muscle and cardiac remodeling in rats with aortic stenosis (AS)-induced HF. Methods: AS was created by placing a stainless-steel clip on the ascending aorta. After clinically detecting HF, GH (2 mg/kg/day) was subcutaneously injected for 14 days (AS-GH group). Results were compared with those from Sham and non-treated AS groups. Transthoracic echocardiogram was performed before and after treatment. Protein expression was evaluated by Western blot and satellite cells activation by immunofluorescence. Statistical analyzes: ANOVA and Tukey or Kruskal-Wallis and Student-Newman-Keuls. Results: Before treatment both AS groups presented a similar degree of cardiac injury. GH prevented body weight loss and attenuated systolic dysfunction. Soleus cross-sectional fiber areas were lower in both AS groups than Sham (Sham 3,556±447; AS 2,882±422; AS-GH 2,868±591 μm 2 ; p=0.016). GH increased IGF-1 serum concentration (Sham 938±83; AS 866±116; AS-GH 1167±166 ng/mL; p<0.0001) and IGF-1 muscle protein expression and activated PI3K protein. Neural cell adhesion molecule (NCAM) immunofluorescence was increased in both AS groups. Catabolism-related intracellular pathways did not differ between groups. Conclusion: Short-term growth hormone attenuates left ventricular systolic dysfunction in rats with aortic stenosis-induced HF. Despite preserving body weight, increasing serum and muscular IGF-1 levels, and stimulating PI3K muscle expression, GH does not modulate soleus muscle trophism, satellite cells activation or intracellular pathways associated with muscle catabolism.