Mitochondrial defects and oxidative damage in patients with peripheral arterial disease

Iraklis I Pipinos, Andrew R. Judge, Zhen Zhu, Joshua T. Selsby, Stanley A. Swanson, Jason M Johanning, Bernard Timothy Baxter, Thomas G. Lynch, Stephen L. Dodd

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)262-269
Number of pages8
JournalFree Radical Biology and Medicine
Volume41
Issue number2
DOIs
StatePublished - Jul 15 2006

Fingerprint

Peripheral Arterial Disease
Oxidative stress
Oxidative Stress
Lipid Peroxides
Glutathione Peroxidase
Muscle
Catalase
Defects
Superoxide Dismutase
Antioxidants
Electron Transport Complex I
Muscles
Proteins
Enzymes
Electron Transport
Respiration
Enzyme activity
Skeletal Muscle
Biomarkers
Lipids

Keywords

  • Humans
  • Intermittent claudication
  • Ischemia
  • Ischemia-reperfusion
  • Metabolism
  • Mitochondria
  • Peripheral arterial disease
  • Reactive oxygen species
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Mitochondrial defects and oxidative damage in patients with peripheral arterial disease. / Pipinos, Iraklis I; Judge, Andrew R.; Zhu, Zhen; Selsby, Joshua T.; Swanson, Stanley A.; Johanning, Jason M; Baxter, Bernard Timothy; Lynch, Thomas G.; Dodd, Stephen L.

In: Free Radical Biology and Medicine, Vol. 41, No. 2, 15.07.2006, p. 262-269.

Research output: Contribution to journalArticle

Pipinos, Iraklis I ; Judge, Andrew R. ; Zhu, Zhen ; Selsby, Joshua T. ; Swanson, Stanley A. ; Johanning, Jason M ; Baxter, Bernard Timothy ; Lynch, Thomas G. ; Dodd, Stephen L. / Mitochondrial defects and oxidative damage in patients with peripheral arterial disease. In: Free Radical Biology and Medicine. 2006 ; Vol. 41, No. 2. pp. 262-269.
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