Lack of beta(2)-adrenoceptors aggravates heart failure-induced skeletal muscle myopathy in mice

Lack of beta(2)-adrenoceptors aggravates heart failure-induced skeletal muscle myopathy in mice

Author Voltarelli, Vanessa A. Google Scholar
Bechara, Luiz R. G. Google Scholar
Bacurau, Aline V. N. Google Scholar
Mattos, Katt C. Google Scholar
Dourado, Paulo M. M. Google Scholar
Bueno, Carlos R. Google Scholar
Casarini, Dulce E. Autor UNIFESP Google Scholar
Negrao, Carlos E. Google Scholar
Brum, Patricia C. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Skeletal myopathy is a hallmark of heart failure (HF) and has been associated with a poor prognosis. HF and other chronic degenerative diseases share a common feature of a stressed system: sympathetic hyperactivity. Although beneficial acutely, chronic sympathetic hyperactivity is one of the main triggers of skeletal myopathy in HF. Considering that (2)-adrenoceptors mediate the activity of sympathetic nervous system in skeletal muscle, we presently evaluated the contribution of (2)-adrenoceptors for the morphofunctional alterations in skeletal muscle and also for exercise intolerance induced by HF. Male WT and (2)-adrenoceptor knockout mice on a FVB genetic background (2KO) were submitted to myocardial infarction (MI) or SHAM surgery. Ninety days after MI both WT and 2KO mice presented to cardiac dysfunction and remodelling accompanied by significantly increased norepinephrine and epinephrine plasma levels, exercise intolerance, changes towards more glycolytic fibres and vascular rarefaction in plantaris muscle. However, 2KO MI mice displayed more pronounced exercise intolerance and skeletal myopathy when compared to WT MI mice. Skeletal muscle atrophy of infarcted 2KO mice was paralleled by reduced levels of phosphorylated Akt at Ser 473 while increased levels of proteins related with the ubiquitin--proteasome system, and increased 26S proteasome activity. Taken together, our results suggest that lack of (2)-adrenoceptors worsen and/or anticipate the skeletal myopathy observed in HF.
Keywords heart failure
skeletal muscle
(2)-adrenoceptors
proteasome
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2008/56483-1
CNPq: 302201/2011-4
FAPESP: 2010/50048-1
Date 2014-06-01
Published in Journal of Cellular and Molecular Medicine. Hoboken: Wiley-Blackwell, v. 18, n. 6, p. 1087-1097, 2014.
ISSN 1582-4934 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 1087-1097
Origin http://dx.doi.org/10.1111/jcmm.12253
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000340390500014
URI http://repositorio.unifesp.br/handle/11600/37795

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