title: Endothelial Cell Bioenergetics and Mitochondrial DNA Damage Differ in Humans Having African or West Eurasian Maternal Ancestry.
abstract: BACKGROUND
  We hypothesized that endothelial cells having distinct mitochondrial genetic backgrounds would show variation in mitochondrial function and oxidative stress markers concordant with known differential cardiovascular disease susceptibilities. To test this hypothesis, mitochondrial bioenergetics were determined in endothelial cells from healthy individuals with African versus European maternal ancestries.
  
  
  RESULTS
  Bioenergetics and mitochondrial DNA (mtDNA) damage were assessed in single-donor human umbilical vein endothelial cells belonging to mtDNA haplogroups H and L, representing West Eurasian and African maternal ancestries, respectively. Human umbilical vein endothelial cells from haplogroup L used less oxygen for ATP production and had increased levels of mtDNA damage compared with those in haplogroup H. Differences in bioenergetic capacity were also observed in that human umbilical vein endothelial cells belonging to haplogroup L had decreased maximal bioenergetic capacities compared with haplogroup H. Analysis of peripheral blood mononuclear cells from age-matched healthy controls with West Eurasian or African maternal ancestries showed that haplogroups sharing an A to G mtDNA mutation at nucleotide pair 10398 had increased mtDNA damage compared with those lacking this mutation. Further study of angiographically proven patients with coronary artery disease and age-matched healthy controls revealed that mtDNA damage was associated with vascular function and remodeling and that age of disease onset was later in individuals from haplogroups lacking the A to G mutation at nucleotide pair 10398.
  
  
  CONCLUSIONS
  Differences in mitochondrial bioenergetics and mtDNA damage associated with maternal ancestry may contribute to endothelial dysfunction and vascular disease.
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: David M
authors.initials: DM
authors.lastname: Krzywanski
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Moellering
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: David G
authors.initials: DG
authors.lastname: Westbrook
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Dunham-Snary
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Jamelle
authors.initials: J
authors.lastname: Brown
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Bray
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Kyle P
authors.initials: KP
authors.lastname: Feeley
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Sammy
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Schurr
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Vita
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ambalavanan
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: David
authors.initials: D
authors.lastname: Calhoun
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.).
authors.forename: Louis
authors.initials: L
authors.lastname: Dell'Italia
authors.affiliation: From the Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (D.M.K.); Department of Nutrition Sciences (D.R.M.), Center for Free Radical Biology and Medicine (D.R.M., D.G.W., K.J.D.-S., J.B., A.W.B., K.P.F., M.J.S., M.R.S., L.D., S.W.B.), Division of Molecular and Cellular Pathology, Department of Pathology (D.G.W., J.B., A.W.B., K.P.F., M.J.S., M.R.S., S.W.B.), Department of Pediatrics (N.A.), Department of Medicine (D.C., L.D.), University of Alabama at Birmingham; Department of Medicine, Queen's University, Kingston, Ontario, Canada (K.J.D.-S.); Department of Anthropology, University of Pennsylvania, Philadelphia (T.G.S.); and Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, MA (J.A.V.). sballing@uab.edu.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Ballinger
mesh_terms: D044383:Black People / Q000235:genetics*; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial
keywords: DNA, mitochondrial; coronary artery disease; endothelial cells; genetics; human umbilical vein endothelial cell; mitochondria