title: Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation.
abstract: Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF.
authors.affiliation: Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin;
authors.forename: Larisa
authors.initials: L
authors.lastname: Emelyanova
authors.affiliation: Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin;
authors.forename: Zain
authors.initials: Z
authors.lastname: Ashary
authors.affiliation: Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin;
authors.forename: Milanka
authors.initials: M
authors.lastname: Cosic
authors.affiliation: Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin;
authors.forename: Ulugbek
authors.initials: U
authors.lastname: Negmadjanov
authors.affiliation: Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin;
authors.forename: Gracious
authors.initials: G
authors.lastname: Ross
authors.affiliation: Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin;
authors.forename: Farhan
authors.initials: F
authors.lastname: Rizvi
authors.affiliation: Patient-Centered Research, Aurora Research Institute, Aurora Health Care, Milwaukee, Wisconsin; and.
authors.forename: Susan
authors.initials: S
authors.lastname: Olet
authors.affiliation: Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin.
authors.forename: David
authors.initials: D
authors.lastname: Kress
authors.affiliation: Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin.
authors.forename: Jasbir
authors.initials: J
authors.lastname: Sra
authors.affiliation: Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin.
authors.forename: A Jamil
authors.initials: AJ
authors.lastname: Tajik
authors.affiliation: Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin;
authors.forename: Ekhson L
authors.initials: EL
authors.lastname: Holmuhamedov
authors.affiliation: Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin;
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin; Patient-Centered Research, Aurora Research Institute, Aurora Health Care, Milwaukee, Wisconsin; and Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, Wisconsin publishing44@aurora.org.
authors.forename: Arshad
authors.initials: A
authors.lastname: Jahangir
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism; D001281:Atrial Fibrillation / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D016022:Case-Control Studies; D018450:Disease Progression; D015536:Down-Regulation; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D005260:Female; D006325:Heart Atria / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D013481:Superoxides / Q000378:metabolism
chemical_list: D000447:Aldehydes; D045222:Electron Transport Chain Complex Proteins; D013481:Superoxides; C027576:4-hydroxy-2-nonenal
keywords: 4-hydroxynonenal protein adducts; atrial fibrillation; electron transport chain complexes; humans; mitochondria; oxidative phosphorylation; oxidative stress; superoxide