title: A novel mechanism for the beneficial vascular effects of high-density lipoprotein cholesterol: enhanced vasorelaxation and increased endothelial nitric oxide synthase expression.
abstract: BACKGROUND
  Low levels of high-density lipoprotein (HDL) cholesterol increase the risk of coronary artery disease (CAD), and recent clinical studies suggest that interventions in low-HDL patients are beneficial. The purpose of this study was to examine the effect of increased HDL levels on endothelium-dependent vasodilation.
  
  
  METHODS
  We studied patients with CAD with a low-density lipoprotein (LDL) level of <100 mg/dL. Patients with an HDL level of < or =36 mg/dL were treated with niacin (n = 11), and patients with an HDL level of >36 mg/dL were followed as controls (n = 10). Baseline and 3-month follow-up studies of flow-mediated dilation (FMD) and blood lipid levels were obtained.
  
  
  RESULTS
  HDL levels increased from 30.1 +/- 1.2 to 40.5 +/- 1.2 mg/dL in the niacin-treated patients (P <.001) but remained unchanged in the control patients. At baseline, FMD was impaired in both the treated (6.5% +/- 1%) and the control (7.3% +/- 1%) patients compared with 10 healthy subjects (16% +/- 2%, P <.01). After 3 months, FMD improved in the niacin-treated patients (11.8% +/- 1%, P =.001) but remained unchanged in the control patients (6.2% +/- 1%). Exposure of cultured human vascular endothelial cells to HDL in vitro enhanced expression of endothelial nitric oxide synthase (eNOS), as shown by immunoblotting.
  
  
  CONCLUSIONS
  In patients with CAD and well-controlled LDL levels, elevation of HDL with niacin improves endothelial function. HDL increases eNOS protein expression in cultured vascular endothelial cells. Taken together, these observations suggest that HDL-mediated increases in eNOS expression may contribute to the observed enhancement in vasorelaxation and thus support a previously unrecognized mechanism for the beneficial cardiovascular effects of HDL.
authors.affiliation: Department of Medicine, New England Medical Center Hospitals, Inc, Tufts University School of Medicine, Boston, Mass, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Kuvin
authors.forename: Maria E
authors.initials: ME
authors.lastname: Rämet
authors.forename: Ayan R
authors.initials: AR
authors.lastname: Patel
authors.forename: Natesa G
authors.initials: NG
authors.lastname: Pandian
authors.forename: Michael E
authors.initials: ME
authors.lastname: Mendelsohn
authors.forename: Richard H
authors.initials: RH
authors.lastname: Karas
mesh_terms: D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000628:therapy; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014665:Vasodilator Agents; D009525:Niacin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III