Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:83009-83021. https://doi.org/10.18632/oncotarget.20583

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Abstract

Aline R.R. Lima1,*, Luana U. Pagan1,*, Ricardo L. Damatto1,*, Marcelo D.M. Cezar1,*, Camila Bonomo1,*, Mariana J. Gomes1,*, Paula F. Martinez2,*, Daniele M. Guizoni1,*, Dijon H.S. Campos1,*, Felipe C. Damatto1,*, Katashi Okoshi1,* and Marina P. Okoshi1,*

1Botucatu Medical School, Internal Medicine Departament, Sao Paulo State University, UNESP, Botucatu, Brazil

2School 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: [email protected]

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 μm2; 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.


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