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Am J Physiol Cell Physiol (May 22, 2002). doi:10.1152/ajpcell.00046.2002
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Articles in PresS, published online ahead of print May 22, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00046.2002
Submitted on January 29, 2002
Accepted on May 17, 2002

L-carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure

Giorgio Vescovo1, Barbara Ravara2, Valerio Gobbo2, Marco Sandri2, Annalisa Angelini3, Mila Della Barbera3, Massimo Dona2, Gianfranco Peluso4, Menotti Calvani5, Luigi Mosconi5, and Luciano Dalla Libera2*

1 Internal Medicine, City Hospital, Adria, Rovigo, Italy
2 Biomedical Sciences, CNR Unit Muscle Biology and Physiopathology, Padova, Padova, Italy
3 Cardiovascular Pathology, University of Padova, Padova, Padova, Italy
4 Experimental Oncology, National Cancer Institute, Napoli, Napoli, Italy
5 Scientific Department, Sigma Tau, Roma, Roma, Italy

* To whom correspondence should be addressed. E-mail: ldl{at}civ.bio.unipd.it.

Skeletal muscle in congestive heart failure is responsible for increased fatigability, decreased exercise capacity and endurance. A specific myopathy with increased expression of fast-type myosins, myocyte atrophy, secondary to myocyte apoptosis triggered by high levels of circulating TNF{alpha} has been described. In an animal model of heart failure, the monocrotaline-treated rat, we have observed an increase of apoptotic skeletal muscle nuclei. Proapoptotic agents, caspases 3 and 9, were increased, as well as serum levels of TNF{alpha} and its second messenger sphingosine. Treatment of rats with L-carnitine, known for its protective effect on muscle metabolism injuries, was found to inhibit caspases, to decrease the levels of TNF{alpha} and sphingosine as well the number of apoptotic myonuclei. Staurosporine was used in in vitro experiments, to induce apoptosis in skeletal muscle cells in culture. When increasing concentrations of L-carnitine were applied to skeletal muscle cells, before staurosporine treatment, we observed a dose-dependent reduction in apoptosis. These findings show that L-carnitine can prevent apoptosis of skeletal muscles cells and can have a role in the treatment of congestive heart failure-associated myopathy.




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