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Gene Responsible for Statin-induced Muscle Pain Identified
November 28, 2007 at 3:29 PM
General Health News
We reasoned that since atrogin-1 plays a key role in the development of wasting in skeletal muscle, it might also mediate part of [patients] sensitivity to statins, the researchers said.
In the study, the scientists proceeded to conduct three separate experiments to test this hypothesis. They first examined the expression of the atrogin-1 gene in biopsies of 19 human quadricep muscles from five control patients, six patients with muscle pain who were not being treated with statins and eight patients with muscle pain/damage who were using statins.
The analysis showed that atrogin-1 expression was significantly higher among the statin users. Next, the scientists studied statins effects on cultured muscle cells treated with various concentrations of lovastatin. Compared with control samples, the lovastatin-treated cells became progressively thinner and more damaged. But the cells lacking the atrogin-1 gene were resistant to statins deleterious effects.
Finally, the authors tested the drug in zebrafish. And, they showed that just as in mammalian muscle cell culture, lovastatin led to muscle damage, even at low concentrations; as the concentration was increased, so too was the damage. And, once again, they observed that fish lacking the atrogin-1 gene were resistant to statin-induced damage. These three complementary experiments demonstrate that atrogin-1 has a fundamental role in statin-induced toxicity, Lecker said.
Future experiments will be aimed at understanding how statins turn on the atrogin-1 response in muscle, and in ascertaining what transpires in muscle following atrogin-1 activation that leads to muscle damage and atrophy. The hope is that eventually patients will be able to glean statins positive benefits to cholesterol metabolism and reduction of cardiovascular events while being spared accompanying muscle toxicities, he said.
The study will be published in The Journal of Clinical Investigation.
Source-ANI
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