title: Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy.
abstract: BACKGROUND
  High-density lipoprotein (HDL)-raising therapies are currently under intense evaluation, but the effects of HDL may be highly heterogeneous. We therefore compared the endothelial effects of HDL from healthy subjects and from patients with type 2 diabetes mellitus and low HDL (meeting the criteria for metabolic syndrome), who are frequently considered for HDL-raising therapies. Moreover, in diabetic patients, we examined the impact of extended-release (ER) niacin therapy on the endothelial effects of HDL.
  
  
  RESULTS
  HDL was isolated from healthy subjects (n=10) and patients with type 2 diabetes (n=33) by sequential ultracentrifugation. Effects of HDL on endothelial nitric oxide and superoxide production were characterized by electron spin resonance spectroscopy analysis. Effects of HDL on endothelium-dependent vasodilation and early endothelial progenitor cell-mediated endothelial repair were examined. Patients with diabetes were randomized to a 3-month therapy with ER niacin (1500 mg/d) or placebo, and endothelial effects of HDL were characterized. HDL from healthy subjects stimulated endothelial nitric oxide production, reduced endothelial oxidant stress, and improved endothelium-dependent vasodilation and early endothelial progenitor cell-mediated endothelial repair. In contrast, these beneficial endothelial effects of HDL were not observed in HDL from diabetic patients, which suggests markedly impaired endothelial-protective properties of HDL. ER niacin therapy improved the capacity of HDL to stimulate endothelial nitric oxide, to reduce superoxide production, and to promote endothelial progenitor cell-mediated endothelial repair. Further measurements suggested increased lipid oxidation of HDL in diabetic patients, and a reduction after ER niacin therapy.
  
  
  CONCLUSIONS
  HDL from patients with type 2 diabetes mellitus and metabolic syndrome has substantially impaired endothelial-protective effects compared with HDL from healthy subjects. ER niacin therapy not only increases HDL plasma levels but markedly improves endothelial-protective functions of HDL in these patients, which is potentially more important.
  
  
  BACKGROUND
  clinicaltrials.gov. Identifier: NCT00346970.
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Sajoscha A
authors.initials: SA
authors.lastname: Sorrentino
authors.forename: Christian
authors.initials: C
authors.lastname: Besler
authors.forename: Lucia
authors.initials: L
authors.lastname: Rohrer
authors.forename: Martin
authors.initials: M
authors.lastname: Meyer
authors.forename: Kathrin
authors.initials: K
authors.lastname: Heinrich
authors.forename: Ferdinand H
authors.initials: FH
authors.lastname: Bahlmann
authors.forename: Maja
authors.initials: M
authors.lastname: Mueller
authors.forename: Tibor
authors.initials: T
authors.lastname: Horváth
authors.forename: Carola
authors.initials: C
authors.lastname: Doerries
authors.forename: Mariko
authors.initials: M
authors.lastname: Heinemann
authors.forename: Stella
authors.initials: S
authors.lastname: Flemmer
authors.forename: Andrea
authors.initials: A
authors.lastname: Markowski
authors.forename: Costantina
authors.initials: C
authors.lastname: Manes
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Bahr
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
mesh_terms: D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D015227:Lipid Peroxidation / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism; D009525:Niacin / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D003692:Delayed-Action Preparations; D005609:Free Radicals; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D013481:Superoxides; D009525:Niacin; D009569:Nitric Oxide; D009195:Peroxidase; D019255:NADPH Oxidases