title: Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms.
abstract: In contrast to the current belief that cholesterol reduction with statins decreases atherosclerosis, we present a perspective that statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and 'heme A', and thereby ATP generation. Statins inhibit the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification. Statins inhibit the biosynthesis of selenium containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress. An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency. Thus, the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs. We propose that current statin treatment guidelines be critically reevaluated.
authors: Nagoya City University and Institute for Consumer Science and Human Life, Kinjo Gakuin University, 2-1723 Omori, Moriyama, Nagoya 463-8521, Japan.
authors: Harumi
authors: H
authors: Okuyama
authors: Peter H
authors: PH
authors: Langsjoen
authors: Tomohito
authors: T
authors: Hamazaki
authors: Yoichi
authors: Y
authors: Ogushi
authors: Rokuro
authors: R
authors: Hama
authors: Tetsuyuki
authors: T
authors: Kobayashi
authors: Hajime
authors: H
authors: Uchino
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D006333:Heart Failure / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D008928:Mitochondria / Q000473:pathology; D017410:Practice Guidelines as Topic; D012643:Selenium / Q000172:deficiency / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D005979:Glutathione Peroxidase; D012643:Selenium
keywords: ATP generation; atherosclerosis; coenzyme Q10; heart failure; mitochondrial toxin; selenoprotein; statin; statin cardiomyopathy; vitamin K2