Molecular basis of statin-associated myopathy.
Coronary artery disease (CAD) constitutes the most common cause of morbidity and mortality in developed countries. Statins effectively reduce low-density lipoprotein cholesterol, an important risk factor for CAD and related acute coronary syndromes. They are an extensively studied group of drugs with versatile properties. Overall, they are safe and effective drugs but their myotoxic potential cannot be overlooked. In this review we focus on the pathogenesis of statins' myopathic side effects. Statins can interfere with protein modification at multiple levels. They can affect protein prenylation, an important post-translational modification of membrane bound proteins. They can also adversely affect selenoprotein synthesis, or can interfere with the biosynthesis of dolichols, which are involved in the process of protein glycosylation. Statin-induced myopathy may be also associated with mitochondrial dysfunction. Statins remain the spearhead of our armamentarium in treating atherosclerotic disease. Consistent with their versatile properties it is anticipated to see in the future their indications to expand. Better understanding of the molecular mechanisms involved in statin-induced myopathy may help identify patient groups susceptible to statins' side effects, thereby increasing their safety.
Vaklavas
Christos
C
Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, USA.
Chatzizisis
Yiannis S
YS
Ziakas
Anthony
A
Zamboulis
Chrysanthos
C
Giannoglou
George D
GD
D050197:Atherosclerosis / Q000188:drug therapy*; D002784:Cholesterol / Q000737:chemistry; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009135:Muscular Diseases / Q000209:etiology* / Q000235:genetics; D011499:Protein Processing, Post-Translational; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014451:Ubiquinone / Q000737:chemistry
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008565:Membrane Proteins; D014451:Ubiquinone; D002784:Cholesterol; D020558:GTP Phosphohydrolases