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Skeletal muscle fibres synthesis in heart failure: role of PGC-1alpha, calcineurin and GH.

Abstract：

BACKGROUND:Patients with congestive heart failure (CHF) have decreased exercise capacity because of muscle fatigability. Symptoms are due to a specific myopathy with increased expression of fast type II fibres, fast MHCs and muscle atrophy. PGC-1alpha, a potent transcriptional coactivator for nuclear receptors, induces mitochondrial myogenesis and the preferential synthesis of slow fibres. IGF1-Calcineurin stimulation can lead to increased expression of PGC-1alpha. METHODS:We investigated the levels of PGC-1alpha during progression and regression of skeletal myopathy in the soleus muscle of rats with right heart failure secondary to monocrotaline-induced pulmonary hypertension. We used GH to stimulate the IGF1-calcineurin-PGC-1alpha axis. RESULTS:The slow MHC1 decreased from 90.6+/-0.5 to 71.7+/-2.2 in the CHF rats (p<0.00001) and increased to 82.1+/-1.8 after GH (p<0.00002). Western blot analysis showed that PGC-1alpha is significantly decreased in CHF, while it came back to control values after GH. Cytochrome c was decreased in CHF and returned to control values with GH. Troponin I was expressed solely as slow isoform in the control soleus, while the fast isoform appeared in CHF. Its expression returned to control values after GH. CONCLUSIONS:We conclude that PGC-1alpha plays an important role in regulating slow fibres expression. PGC1-1alpha is in turn regulated by the IGF1-calcineurin axis. GH by increasing the circulating levels of IGF1, enhanced the expression of slow MHC1, TnI and the synthesis of mitochondria.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Vescovo G,Ravara B,Gobbo V,Angelini A,Dalla Libera L

doi

10.1016/j.ijcard.2004.10.059

subject

Has Abstract

pub_date

2005-10-10 00:00:00

pages

298-306

issue

3

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(05)00181-6

journal_volume

104

pub_type

杂志文章

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