title: Human leukocyte/endothelial cell interactions and mitochondrial dysfunction in type 2 diabetic patients and their association with silent myocardial ischemia.
abstract: OBJECTIVE
  Diabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed.
  
  
  METHODS
  Mitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition- and age-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed.
  
  
  RESULTS
  Waist, levels of triglycerides, proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α), HbA1c, high-sensitivity C-reactive protein (hs-CRP), glucose, and insulin, and homeostasis model assessment of insulin resistance were higher in diabetic patients than in control subjects. However, no statistical differences in hs-CRP and insulin levels were detected when the data were adjusted for waist. None of these parameters varied between SMI and non-SMI patients. Mitochondrial function was impaired and leukocyte-endothelium interactions were more frequent among diabetic patients, which was evident in the lower mitochondrial O2 consumption, membrane potential, polymorphonuclear cell rolling velocity, and GSH/GSSG ratio, and in the higher mitochondrial reactive oxygen species production and rolling flux, adhesion, and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin molecules observed in these subjects. Moreover, these differences correlated with SMI. Statistical differences were maintained after adjusting the data for BMI and waist, with the exception of VCAM-1 levels when adjusted for waist.
  
  
  CONCLUSIONS
  Oxidative stress, mitochondrial dysfunction, and endothelium-inducing leukocyte-endothelium interactions are features of type 2 diabetes and correlate with SMI.
authors.affiliation: Service of Endocrinology, University Hospital Doctor Peset, Valencia, Spain. hernandez_antmij@gva.es
authors.forename: Antonio
authors.initials: A
authors.lastname: Hernandez-Mijares
authors.forename: Milagros
authors.initials: M
authors.lastname: Rocha
authors.forename: Susana
authors.initials: S
authors.lastname: Rovira-Llopis
authors.forename: Celia
authors.initials: C
authors.lastname: Bañuls
authors.forename: Lorena
authors.initials: L
authors.lastname: Bellod
authors.forename: Carmen
authors.initials: C
authors.lastname: de Pablo
authors.forename: Angeles
authors.initials: A
authors.lastname: Alvarez
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Roldan-Torres
authors.forename: Eva
authors.initials: E
authors.lastname: Sola-Izquierdo
authors.forename: Victor M
authors.initials: VM
authors.lastname: Victor
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D002097:C-Reactive Protein; D019803:Glutathione Disulfide