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Arch Biochem Biophys. 2018 Jan 1;637:64-72. doi: 10.1016/j.abb.2017.12.003. Epub 2017 Dec 5.

Atorvastatin affects negatively respiratory function of isolated endothelial mitochondria.

Author information

1
Department of Bioenergetics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznan, Poland.
2
Department of Bioenergetics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznan, Poland. Electronic address: wiesiaj@amu.edu.pl.

Abstract

The purpose of this research was to elucidate the direct effects of two popular blood cholesterol-lowering drugs used to treat cardiovascular diseases, atorvastatin and pravastatin, on respiratory function, membrane potential, and reactive oxygen species formation in mitochondria isolated from human umbilical vein endothelial cells (EA.hy926 cell line). Hydrophilic pravastatin did not significantly affect endothelial mitochondria function. In contrast, hydrophobic calcium-containing atorvastatin induced a loss of outer mitochondrial membrane integrity, an increase in hydrogen peroxide formation, and reductions in maximal (phosphorylating or uncoupled) respiratory rate, membrane potential and oxidative phosphorylation efficiency. The atorvastatin-induced changes indicate an impairment of mitochondrial function at the level of ATP synthesis and at the level of the respiratory chain, likely at complex I and complex III. The atorvastatin action on endothelial mitochondria was highly dependent on calcium ions and led to a disturbance in mitochondrial calcium homeostasis. Uptake of calcium ions included in atorvastatin molecule induced mitochondrial uncoupling that enhanced the inhibition of the mitochondrial respiratory chain by atorvastatin. Our results indicate that hydrophobic calcium-containing atorvastatin, widely used as anti-atherosclerotic agent, has a direct negative action on isolated endothelial mitochondria.

KEYWORDS:

Atorvastatin; Endothelial mitochondria; Membrane potential; Pravastatin; Reactive oxygen species; Respiration

PMID:
29217137
DOI:
10.1016/j.abb.2017.12.003
[Indexed for MEDLINE]

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