Plasminogen activator inhibitor-1 in patients with Kawasaki disease: diagnostic value for the prediction of coronary artery lesion and implication for a new mode of therapy.
Kawasaki disease (KD) in children takes the form of acute systemic vasculitis, which causes coronary artery dilation and aneurysm formation in 10% to 15% of the patients. We have recently shown that matrix metalloproteinases (MMPs) are intimately involved in coronary arterial wall destruction and the resultant formation of coronary artery lesions (CALs) in this disease. Plasminogen activators (PAs) are known to be a major pathway of MMP activation, and this suggests that their inhibitor, plasminogen activator inhibitor-1 (PAI-1), also plays important roles in the development of CALs in KD. The present study was conducted to test the hypothesis that circulating levels of PAI-I are related to CAL formation in KD. Plasma levels of PAI-1 were measured by enzyme-linked immunoassay in 37 KD patients without CALs (group 1) and 7 KD patients with CALs (group 2). Blood samples were obtained before and after i.v. gammaglobulin therapy (IVGG), and in the convalescent stage. Levels of PAI-1 were significantly higher in KD patients before IVGG than in 18 age-matched healthy control subjects (p < 0.01). More importantly, both pre-IVGG and post-IVGG levels of PAI-1 were significantly higher in group 2 than in group 1 (p < 0.01). Furthermore, PAI-1 levels of 9 patients from group 1 who showed pre-IVGG PAI-1 levels higher than the minimum PAI-1 level in group 2 significantly decreased after IVGG, whereas PAI-1 levels of group 2 patients remained persistently elevated, further suggesting a close association between PAI-1 and CAL development in KD. Thus, PAI-1 may be useful as a predictive marker for CAL development in KD. Studies of the effects of PA inhibition on coronary outcome may provide evidence that PA is a viable therapeutic target for the prevention of KD-related CALs.
Senzaki
Hideaki
H
Department of Pediatric Cardiology and Pediatrics, Saitama Heart Institute, Saitama Medical School Hospital, 38 Morohongo, Moroyama, Saitama 350, Japan. hsenzaki@saitama-med.ac.jp
Kobayashi
Toshiki
T
Nagasaka
Hironori
H
Nakano
Hirofumi
H
Kyo
Shunei
S
Yokote
Yuji
Y
Sasakid
Nozomu
N
D003331:Coronary Vessels / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009080:Mucocutaneous Lymph Node Syndrome / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1