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RESEARCH ARTICLE

Effects of extensively oxidized low-density lipoprotein on mitochondrial function and reactive oxygen species in porcine aortic endothelial cells

¹University of Manitoba

Submitted 10 July 2009 ; revised 13 October 2009 ; accepted in final form 18 October 2009

Atherosclerotic cardiovascular disease is the leading cause of mortality in the Western world. Dysfunction of mitochondrial respiratory chain and overproduction of reactive oxygen species (ROS) are associated with atherosclerosis and cardiovascular disease. Oxidation increases the atherogenecity of LDL. Oxidized LDL may be apoptotic or non-apoptotic for vascular endothelial cells (EC) depending on the intensity of oxidation. A previous study demonstrated that non-apoptotic oxidized LDL increased activity of mitochondrial Complex I in human umbilical vein EC. The present study examined the impact of extensively oxidized LDL (eoLDL) on oxygen consumption and the activities of key enzymes in the mitochondrial respiratory chain of cultured porcine aortic EC. EoLDL significantly reduced oxygen consumption in various mitochondrial complexes detected using oxygraphy. Treatment with eoLDL significantly decreased the activities of NADH-ubiquinone dehydrogenase (Complex I), succinate cytochrome c reductase (Complex II/III), ubiquinone cytochrome c reductase (Complex III) and cytochrome c oxidase (Complex IV), and the levels of NAD+/NADH ratio in EC compared to mildly oxidized LDL, LDL or vehicle. Butylated hydroxytoluene, a potent antioxidant, normalized eoLDL-induced reductions in the activities of Complex I and III enzymes in EC. Mitochondria-associated intracellular ROS and the release of ROS from EC were significantly increased following eoLDL treatment. These findings suggest that eoLDL impairs activities of enzymes in mitochondrial respiratory chain complexes, and increases ROS generation from mitochondria of arterial EC. Collectively, these effects could contribute to vascular injury and atherogenesis under hypercholesterolemia and oxidative stress.

Oxidized lipoproteins; Oxidative stress; Oxygen consumption; Enzymes of mitochondrial respiratory chain