Molecular basis for statin-induced muscle toxicity: implications and possibilities.
Statins are widely used to treat hypercholesterolemia, a known risk factor for atherosclerosis. These drugs can lead to a number of side effects in muscle, including rhabdomyolysis; however, the mechanism of muscle injury is poorly defined. We review the clinical characteristics of this diverse syndrome, as well as the biochemical mechanisms that might provide an explanation for the toxicity of these agents. New findings implicating atrogin-1, a gene required for muscle atrophy, in the pathophysiology of statin-induced muscle injury are discussed, as well as implications of these novel discoveries.
Buettner
Catherine
C
General Medicine and Primary Care, Atrium Suite 1, Shapiro 1, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue Boston, MA 02215, USA. cbuettne@bidmc.harvard.edu
Lecker
Stewart H
SH
D000818:Animals; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D009133:Muscular Atrophy / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009124:Muscle Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases