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

• Published in: Journal of rheumatology Vol. 30; no. 7; pp. 1479 - 1484
• Main Authors: TAM, Lai-Shan, FAN, Boli, LI, Edmund K, THOMAS, G. Neil, YIM, So F, HAINES, Christopher J, TOMLINSON, Brian
• Format: Journal Article
• Language: English
• Published: Toronto, ON The Journal of Rheumatology 01-07-2003; Journal of Rheumatology Publishing
• Subjects: Acute Disease; Administration, Oral; Adult; Biological and medical sciences; 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; Medical sciences; Methionine - administration & dosage; Methionine - pharmacology; Plasminogen Activator Inhibitor 1 - blood; Platelet Activation; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Vasodilation - drug effects; von Willebrand Factor - analysis; Human; Immunopathology; Connective tissue disease; Flow cytometry; Skin disease; Biochemical analysis; Pathophysiology; Cardiovascular disease; Autoimmune disease; Activation; Immune regulation; Endothelium; Vascular disease; Platelet; Systemic disease; Atherosclerosis; Platelet function; Lupus erythematosus; Hyperhomocysteinemia; Disseminated; PLATELET ACTIVATION ENDOTHELIAL DYSFUNCTION HYPERHOMOCYSTEINEMIA SYSTEMIC LUPUS ERYTHEMATOSUS
• ISSN: 0315-162X; 1499-2752

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.