Abstract: Patients with Systemic Lupus Erythematosus Show Increased Platelet Activation and Endothelial Dysfunction Induced by Acute Hyperhomocysteinemia

Patients with Systemic Lupus Erythematosus Show Increased Platelet Activation and Endothelial Dysfunction Induced by Acute Hyperhomocysteinemia

LAI-SHAN TAM, BOLI FAN, EDMUND K. LI, G. NEIL THOMAS, SO F. YIM, CHRISTOPHER J. HAINES, and BRIAN TOMLINSON

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

Key Indexing Terms:

PLATELET ACTIVATION
ENDOTHELIAL DYSFUNCTION
HYPERHOMOCYSTEINEMIA
SYSTEMIC LUPUS ERYTHEMATOSUS

From the Department of Medicine and Therapeutics and Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.

L.S. Tam, MRCP(UK), Medical Officer; B. Fan, PhD, Post-doctorate Fellow; E.K. Li, FRCPC, Associate Professor; G.N. Thomas, PhD, Post-doctorate Fellow, Department of Medicine and Therapeutics; S.F. Yim, MRCOG, Senior Medical Officer; C.J. Haines, FRANZCOG, Professor, Department of Obstetrics and Gynecology; B. Tomlinson, FACP, Professor, Department of Medicine and Therapeutics.

Address reprint requests to Dr. L.S. Tam, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. E-mail: tamls_813@yahoo.com

Submitted June 27, 2002; revision accepted December 16, 2002.