title: Effects of electronegative VLDL on endothelium damage in metabolic syndrome.
abstract: OBJECTIVE
  Biochemical heterogeneity governs functional disparities among lipoproteins. We examined charge-defined VLDL subfractions in metabolic syndrome (MetS) to determine whether their increased electronegativity is associated with increased cytotoxicity and whether high concentrations of highly electronegative subfractions render VLDL harmful to the vascular endothelium.
  
  
  METHODS
  Plasma VLDL of normal individuals (control subjects) (n = 13) and of those with MetS (n = 13) was resolved into subfractions with increasing negative charge (V1-V5) by anion-exchange chromatography. Human aortic endothelial cells were treated with V1-V5 or unfractionated VLDL.
  
  
  RESULTS
  Compared with the control subjects, individuals with MetS had a significantly higher percentage of V5 VLDL (V5/VLDL%) (34 ± 20 vs. 39 ± 11%, respectively; P < 0.05) and plasma V5 concentration ([V5]) (5.5 ± 4.4 vs. 15.2 ± 8.5 mg/dL, respectively; P < 0.001). Apolipoprotein (apo)B100 levels decreased and apoC levels increased from V1 to V5, indicating that V5 is apoC-rich VLDL. Regression analyses of all 26 individuals showed that [V5] was positively correlated with total cholesterol (P = 0.016), triglyceride (P < 0.000001), and V5/VLDL% (P = 0.002). Fasting plasma glucose, but not waist circumference, exhibited a positive trend (P = 0.058); plasma HDL cholesterol exhibited a weak inverse trend (P = 0.138). V5 (10 μg/mL) induced apoptosis in ~50% of endothelial cells in 24 h. V5 was the most rapidly (<15 min) internalized subfraction and induced the production of reactive oxygen species (ROS) in endothelial cells after 20 min. Unfractionated MetS VLDL, but not control VLDL, also induced ROS production and endothelial cell apoptosis.
  
  
  CONCLUSIONS
  In populations with increased risk of diabetes, the vascular endothelium is constantly exposed to VLDL that contains a high proportion of V5. The potential impact of V5-rich VLDL warrants further investigation.
authors.affiliation: Texas Heart Institute, Houston, Texas, USA. cchen@heart.thi.tmc.edu
authors.forename: Chu-Huang
authors.initials: CH
authors.lastname: Chen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lu
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Chen
authors.forename: Roger Y
authors.initials: RY
authors.lastname: Huang
authors.forename: H Ramazan
authors.initials: HR
authors.lastname: Yilmaz
authors.forename: Jianwen
authors.initials: J
authors.lastname: Dong
authors.forename: MacArthur A
authors.initials: MA
authors.lastname: Elayda
authors.forename: Richard A F
authors.initials: RA
authors.lastname: Dixon
authors.forename: Chao-Yuh
authors.initials: CY
authors.lastname: Yang
mesh_terms: D000328:Adult; D015243:Cholesterol, VLDL / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged
chemical_list: D015243:Cholesterol, VLDL