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Skeletal myopathy is a known statin\u2010induced adverse effect associated with mitochondrial changes. We hypothesized that similar effects would occur in cardiac myocytes in a lipophilicity\u2010dependent manner between 2 common statins: atorvastatin (lipophilic) and pravastatin (hydrophilic). Neonatal cardiac ventricular myocytes were treated with atorvastatin and pravastatin for 48 h. Both statins induced endoplasmic reticular (ER) stress, but only atorvastatin inhibited ERK1\/2\n                    <jats:sup>T202\/Y204<\/jats:sup>\n                    , Akt\n                    <jats:sup>Ser473<\/jats:sup>\n                    , and mammalian target of rapamycin signaling; reduced protein abundance of caveolin\u20101, dystrophin, epidermal growth factor receptor, and insulin receptor\u2010\u03b2; decreased Ras homolog gene family member A activation; and induced apoptosis. In cardiomyocyte\u2010equivalent HL\u20101 cells, atorvastatin, but not pravastatin, reduced mitochondrial oxygen consumption. When male mice underwent atorvastatin and pravastatin administration\n                    <jats:italic>per os<\/jats:italic>\n                    for up to 7 mo, only long\u2010term atorvastatin, but not pravastatin, induced elevated serum creatine kinase; swollen, misaligned, size\u2010variable, and disconnected cardiac mitochondria; alteration of ER structure; repression of mitochondria\u2010 and endoplasmic reticulum\u2013related genes; and a 21% increase in mortality in cardiac\u2010specific vinculin\u2010knockout mice during the first 2 months of administration. To our knowledge, we are the first to demonstrate\n                    <jats:italic>in vivo<\/jats:italic>\n                    that long\u2010term atorvastatin administration alters cardiac ultrastructure, a finding with important clinical implications.\u2014\u2014Godoy, J. C., Niesman, I. R., Busija, A.R., Kassan, A., Schilling, J. M., Schwarz, A., Alvarez, E. A., Dalton, N. D., Drummond, J. C., Roth, D.M., Kararigas, G., Patel, H. H., Zemljic\u2010Harpf, A. E. Atorvastatin, but not pravastatin, inhibits cardiac Akt\/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes. FASEB J. 33, 1209\u20131225 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201800876r","type":"journal-article","created":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T16:02:54Z","timestamp":1535731374000},"page":"1209-1225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Atorvastatin, but not pravastatin, inhibits cardiac Akt\/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes"],"prefix":"10.1096","volume":"33","author":[{"given":"Joseph C.","family":"Godoy","sequence":"first","affiliation":[{"name":"Veterans Affairs San Diego Healthcare System  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid 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