Patients with systemic lupus erythematosus show increased platelet activation and endothelial dysfunction induced by acute hyperhomocysteinemia

J Rheumatol. 2003 Jul;30(7):1479-84.

Abstract

Objective: Hyperhomocysteinemia adversely affects the endothelium, although the exact mechanism is unclear. Systemic lupus erythematosus (SLE) is an inflammatory disease with a high atherothrombotic tendency. We examined whether acute hyperhomocysteinemia exacerbates endothelial and platelet dysfunction in patients with SLE.

Methods: Twelve SLE patients and 15 controls were recruited. Oral methionine was used to achieve acute hyperhomocysteinemia. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery; also assessed were the levels of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1). Platelet activation was assessed by the levels of beta-thromboglobulin (beta-TG), fibrinogen binding, and P-selectin expression using flow cytometry.

Results: After oral methionine loading, vWF levels increased significantly, whereas FMD remained unchanged in both groups. PAI-1 increased significantly only in controls. Fibrinogen binding to platelets increased significantly only in SLE patients. Beta-TG remained unchanged in SLE patients but increased significantly in controls. Platelet P-selectin expression did not change in either group.

Conclusion: These results suggest that the prothrombotic tendency after acute hyperhomocysteinemia is mediated by endothelial dysfunction and platelet activation in patients with SLE and healthy controls.

MeSH terms

  • Acute Disease
  • Administration, Oral
  • Adult
  • Brachial Artery / drug effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Female
  • Flow Cytometry
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / physiopathology*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / physiopathology*
  • Male
  • Methionine / administration & dosage
  • Methionine / pharmacology
  • Plasminogen Activator Inhibitor 1 / blood
  • Platelet Activation*
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Vasodilation* / drug effects
  • von Willebrand Factor / analysis

Substances

  • Plasminogen Activator Inhibitor 1
  • von Willebrand Factor
  • Methionine