Abstract 17772: Lack of 2-adrenoceptors Accelerates Skeletal Muscle Atrophy in Myocardial Infarcted Mice: Role of Ubiquitin-Proteasome System and Akt/mTOR Pathway
Although heart failure (HF) is a syndrome of cardiac origin, it promotes changes in other tissues, such as skeletal muscle, where modifications of muscle phenotype and the loss of skeletal muscle mass observed in HF contribute to poor prognosis and increased mortality of patients. Taking into consideration that β2-adrenoceptors mediate the activity of sympathetic nervous system in skeletal muscle and that sympathetic hyperactivity is one of the main components involved in developing skeletal muscle abnormalities in HF, it has been suggested that β2-adrenoceptors would be associated with morphofunctional alterations due to chronic sympathetic hyperactivity in skeletal muscles in HF. In the present study, we evaluated the contribution of β2-adrenoceptors on metabolic and morphofunctional alterations in skeletal muscle and also on exercise intolerance-induced by HF. For this, we used FVB mice and mice lacking β2-adrenoceptors (β2KO) that were submitted to myocardial infarction or sham surgery. Myocardial infarction induced cardiac dysfunction and remodeling in FVB mice, which was accompanied by significantly increased plasma levels of norepinephrine and epinephrine, exercise intolerance, changes in muscle fiber type and vascular rarefaction in both soleus and plantaris muscles. These same responses were observed in mice lacking β2-adrenoceptors submitted to myocardial infarction. However, infarcted β2KO mice presented a higher decrease of exercise tolerance and more severe skeletal myopathy. Accompanying the skeletal muscle atrophy of infarcted β2KO mice, it was observed a significantly increased protein expression of proteins related with the ubiquitin-proteasome system, an increased 26S-proteassome activity and a trend toward decreased protein expression of p-Akt (ser473), p-4E-BP1 (thr37/46) and p-FoxO3a (ser253). These results suggest that the lack of β2-adrenoceptors worsens and/or anticipates the skeletal muscle alterations observed in HF, mainly muscular atrophy, and the activation of ubiquitin-proteassome system and inhibition of protein synthesis by Akt/4E-BP1 pathway seem to play an important role in skeletal muscle myopathy.
- © 2012 by American Heart Association, Inc.