A Novel Mechanism for the Beneficial Vascular Effects of High-Density Lipoprotein Cholesterol: Enhanced Vasorelaxation and Increased Endothelial Nitric Oxide Synthase Expression

Am Heart J. 2002 Jul;144(1):165-72. doi: 10.1067/mhj.2002.123145.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Case-Control Studies
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / therapy
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiology*
  • Female
  • Humans
  • Hypolipidemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Niacin / therapeutic use*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type III
  • Vasodilation / physiology*
  • Vasodilator Agents / therapeutic use*


  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hypolipidemic Agents
  • Vasodilator Agents
  • Niacin
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III