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


CONCLUSIONS
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.
Tam
Lai-Shan
LS
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin. tamls_813@yahoo.com
Fan
Boli
B
Li
Edmund K
EK
Thomas
G Neil
GN
Yim
So F
SF
Haines
Christopher J
CJ
Tomlinson
Brian
B
D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D001916:Brachial Artery / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000503:physiopathology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D015539:Platelet Activation; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects; D014841:von Willebrand Factor / Q000032:analysis
D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D008715:Methionine