Effect of angiotensin-converting enzyme inhibitor on matrix metalloproteinase-9 activity in patients with Kawasaki disease.
BACKGROUND
Matrix metalloproteinase (MMP)-9 is thought to be involved in coronary artery aneurysms (CAAs) in patients with Kawasaki disease (KD); however, MMP-9 inhibitors are not used clinically. This study investigated whether the angiotensin-converting enzyme (ACE) inhibitor captopril could inhibit serum MMP-9 activity using serum from KD patients in an in vitro experiment.


METHODS
In 7 KD patients, serum MMP-9 activity was measured using the MMP-9 assay kit 3 times: before and after intravenous immunoglobulin (IVIG) treatment, and during the convalescent phase. The effect of captopril on MMP-9 activity was also assessed using serum obtained before IVIG treatment.


RESULTS
Serum MMP-9 activity was significantly higher during the pre-treatment phase than during the post-treatment and convalescent phases. MMP-9 activity during the pre-treatment phase was dose-dependently inhibited by captopril, and the IC(50) for MMP-9 was 500nM. The potency of captopril for MMP-9 inhibition was comparable to that for ACE inhibition.


CONCLUSIONS
ACE inhibitor may be effective for preventing CAA formation in KD patients, especially IVIG non-responders.
Inoue
Nao
N
Department of Pharmacology, Osaka Medical College, Takatsuki 569-8686, Japan.
Takai
Shinji
S
Jin
Denan
D
Okumura
Kenichi
K
Okamura
Naoyuki
N
Kajiura
Mitsugu
M
Yoshikawa
Sosuke
S
Kawamura
Naohisa
N
Tamai
Hiroshi
H
Miyazaki
Mizuo
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D020780:Matrix Metalloproteinase 9