Mitochondrial defects and oxidative damage in patients with peripheral arterial disease.
Abnormal mitochondrial function is present in patients with peripheral arterial disease and may contribute to its clinical manifestations. However, the specific biochemical mitochondrial defects and their association with increased oxidative stress have not been fully characterized. Gastrocnemius muscle was obtained from peripheral arterial disease patients (n = 25) and age-matched controls (n = 16) and mitochondrial parameters were measured. Complexes I through IV of the electron transport chain were individually evaluated to assess for isolated defects. Muscle was also evaluated for protein and lipid oxidative changes by measuring the levels of protein carbonyls, lipid hydroperoxides, and total 4-hydroxy-2-nonenal binding and for the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. Mitochondrial electron transport chain complexes I, III, and IV in arterial disease patients demonstrated significant reductions in enzymatic activities and mitochondrial respiration compared to controls. Oxidative stress biomarker analysis demonstrated significantly increased levels of protein carbonyls, lipid hydroperoxides, and 4-hydroxy-2-nonenal compared to control muscle. Antioxidant enzyme activities were altered, with a significant decrease in superoxide dismutase activity and significant increases in catalase and glutathione peroxidase. Peripheral arterial disease is associated with abnormal mitochondrial function and evidence of significant oxidative stress.
Pipinos
Iraklis I
II
Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA. ipipinos@unmc.edu
Judge
Andrew R
AR
Zhu
Zhen
Z
Selsby
Joshua T
JT
Swanson
Stanley A
SA
Johanning
Jason M
JM
Baxter
Bernard T
BT
Lynch
Thomas G
TG
Dodd
Stephen L
SL
D000368:Aged; D016022:Case-Control Studies; D002374:Catalase / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress; D016491:Peripheral Vascular Diseases / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism
D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase