Growth hormone attenuates skeletal muscle changes in experimental chronic heart failure.
OBJECTIVE
This study evaluated the effects of growth hormone (GH) on morphology and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats with ascending aortic stenosis (AAS) induced chronic heart failure.


METHODS
Male 90-100g Wistar rats were subjected to thoracotomy. AAS was created by placing a stainless-steel clip on the ascending aorta. Twenty five weeks after surgery, rats were treated with daily subcutaneous injections of recombinant human GH (2mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated animals served as controls. Left ventricular (LV) function was assessed before and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia, soleus muscle was frozen in liquid nitrogen. Histological sections were stained with HE and picrosirius red to calculate muscle fiber cross-sectional area and collagen fractional area, respectively. MRF myogenin and MyoD expression was analyzed by reverse transcription PCR.


RESULTS
Body weight was similar between groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular (LV) hypertrophy (LV mass index: Control 1.90+/-0.15; AAS 3.11+/-0.44; AAS-GH 2.94+/-0.47 g/kg; p<0.05 AAS and AAS-GH vs. Control), and reduced LV posterior wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS than in Control and AAS-GH groups; there was no difference between AAS-GH and Control groups. Collagen fractional area was significantly higher in AAS than Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1 levels decreased in AAS compared to Control. MyoD mRNA was significantly higher in AAS-GH than AAS; there was no difference between AAS-GH and Control groups. Myogenin mRNA levels were similar between groups.


CONCLUSIONS
In rats with aortic stenosis-induced heart failure, growth hormone administration increases MyoD gene expression above non-treated animal levels, preserves muscular trophism and attenuates interstitial fibrosis. These results suggest that growth hormone may have a potential role as an adjuvant therapy for chronic heart failure.
Santos
Denis Pioli dos
DP
Department of Morphology, Bioscience Institute, São Paulo State University, Botucatu, São Paulo, Brazil.
Okoshi
Katashi
K
Moreira
Vanessa O
VO
Seiva
Fábio R F
FR
Almeida
Fernanda Losi Alves de
FL
Padovani
Carlos Roberto
CR
Carvalho
Robson Francisco
RF
Okoshi
Marina Politi
MP
Cicogna
Antônio Carlos
AC
Castro
Ana Valéria Barros
AV
Pai-Silva
Maeli Dal
MD
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004452:Echocardiography; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D006333:Heart Failure / Q000097:blood / Q000473:pathology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010919:Placebos; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D010919:Placebos; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone