Asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans

Jason R. Chan, Rainer H. Böger, Stefanie M. Bode-Böger, Oranee Tangphao, Philip S. Tsao, Terrence F. Blaschke, John P. Cooke

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is elevated in hypercholesterolemia. This study was designed to determine the role of ADMA in the increased mononuclear cell adhesiveness observed in human hypercholesterolemia. In patient studies, plasma ADMA levels were determined by high-performance liquid chromatography. Functional mononuclear leukocyte adhesion assays were performed in parallel, and flow cytometry was used to characterize bound monocytes and T lymphocytes. Hypercholesterolemic patients were then placed on an oral L-arginine regimen of 14 or 21 g/d and studied over 12 weeks. In cell culture studies, bovine aortic endothelial cells were incubated with varied concentrations of ADMA. Monocytoid cells were cocultured with these bovine aortic endothelial cells, and their adhesiveness was assessed by use of a binding assay. Flow cytometry was used to quantify adhesion molecule expression. Plasma ADMA levels and adhesiveness of mononuclear cells (specifically, monocytes and T lymphocytes) were elevated in hypercholesterolemic patients. Adhesiveness was inversely correlated with the plasma L-arginine/ADMA ratio. Oral administration of L- arginine normalized plasma L-arginine/ADMA ratios and attenuated monocyte and T-lymphocyte adhesiveness. ADMA had no direct effect on the adhesiveness of mononuclear cells. However, monocytes became hyperadhesive when cocultured with ADMA-exposed endothelial cells. In human hypercholesterolemia, the plasma L-arginine/ADMA ratio is inversely correlated with mononuclear cell adhesiveness. Restoration of the L-arginine/ADMA ratio to control levels normalizes mononuclear cell adhesiveness. Our studies suggest that the elaboration of endothelium-derived nitric oxide affects the behavior of circulating T lymphocytes and monocytes.

Original languageEnglish (US)
Pages (from-to)1040-1046
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume20
Issue number4
DOIs
StatePublished - Apr 2000

Keywords

  • Atherosclerosis
  • Endothelium
  • L-arginine
  • Monocytes
  • T lymphocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans'. Together they form a unique fingerprint.

Cite this