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Atorvastatin‐induced cardiac function impairment
Author(s) -
Qiao Congzhen,
Lauver Dale Adam,
Lucchesi Benedict
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.652.17
Subject(s) - atorvastatin , statin , myalgia , medicine , cardiac function curve , heart failure , coenzyme a , hmg coa reductase , cardiac muscle , endocrinology , cholesterol , reductase , cardiology , pharmacology , chemistry , biochemistry , enzyme
Statins, known as 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors, are reported to reduce low‐density lipoprotein cholesterol levels in blood. In spite of the dramatic cholesterol‐lowering effect, statin‐induced myalgia and fatigue have been widely reported. The inhibition of HMG‐CoA reductase by statins prevents the synthesis of mevalonate, a precursor for the synthesis of cholesterol as well as coenzyme Q 10 (CoQ 10 ). It has been well documented that CoQ 10 plays a critical role in the synthesis of mitochondrial adenosine‐5′‐triphosphate (ATP), the depletion of which can cause a reduction of intracellular ATP, leading to myalgia. Given the high‐energy demand that cardiac muscle requires, we are interested in statin's off‐target effect on the skeletal and cardiac muscle in rabbits. Several clinical studies have shown that there is a link between the reduction of CoQ 10 and cardiomyopathy. In addition, endomyocardial biopsies have shown a decrease of myocardial ATP in a failing heart, suggesting that the reduction of ATP may exacerbate heart failure and contribute to heart remodeling. However, few publications have reported the adverse cardiac effects of statins most likely due to the depletion of ATP. To address this issue, we demonstrated atorvastatin's effect on rabbit cardiac function by employing Langendorff heart model as well as morphological changes detected by transmission electronic microscopy. Our preliminary data suggest that atorvastatin impairs cardiac function in 7 and 28 days treatment compared to placebos. In addition, the disruption of the mitochondrial ultrastructure in 28 days atorvastatin‐treated group indicates a long‐term deleterious cardiac effect of atorvastatin. Hence, we believe that statin‐induced CoQ 10 deficiency leads to the depletion of ATP, which impairs heart function and may contributes to the pathogenesis of heart failure. The source of research support: the University of Michigan Cardiovascular Research Fund