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

Author(s):Show less -

Lima, Aline R. R. ^[1] ; Pagan, Luana U. ^[1] ; Damatto, Ricardo L. ^[1] ; Cezar, Marcelo D. M. ^[1] ; Bonomo, Camila ^[1] ; Gomes, Mariana J. ^[1] ; Martinez, Paula F. ^[2] ; Guizoni, Daniele M. ^[1] ; Campos, Dijon H. S. ^[1] ; Damatto, Felipe C. ^[1] ; Okoshi, Katashi ^[1] ; Okoshi, Marina P. ^[1]

Affiliation

^[1] Sao Paulo State Univ, Botucatu Med Sch, Internal Med Dept, UNESP, Botucatu, SP - Brazil

^[2] Univ Fed Mato Grosso do Sul, Sch Phys Therapy, Campo Grande - Brazil

• Document type: Journal article
• Source: ONCOTARGET; v. 8, n. 47, p. 83009-83021, OCT 10 2017.
• Web of Science Citations: 2

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 mu m(2); p=0.016). GH increased IGF1 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. (AU)

• FAPESP's process: 09/54102-3 - Acquisition of an ultracentrifuge and an echocardiograph to equip a Centralized Multi-User Laboratory
• Grantee: Marina Politi Okoshi
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 12/50512-5 - Effects of physical training on throphism and myostatin/follistatin pathway in skeletal and cardiac muscle of spontaneously hypertensive rats with heart failure
• Grantee: Marina Politi Okoshi
• Support Opportunities: Regular Research Grants