Abnormal Matrix Remodeling in Adolescents and Young Adults with Kawasaki Disease Late after Onset

Abstract

Patients with a history of Kawasaki disease (KD), have been found to have pericoronary and myocardial fibrosis. Serum biomarkers of fibrosis may be sensitive indices for detection of these late cardiac complications in KD patients. We studied a cohort of 60 adolescents and young adults comprising 10 KD patients with persistent coronary artery lesions (CAL) occurring at a mean (SD) time of 14.5 (4.4) years after disease onset, 25 KD patients with no CAL after disease onset, and 25 healthy age-matched volunteers. We compared laboratory data from the patients and volunteers, including lipid profile, liver function, amino-terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), and MMP-9:TIMP-1 ratios. Severity of CAL was determined on the basis of computed tomography determinations of the frequency of aneurysms and the extent of coronary stenosis/occlusion, thrombosis, and calcification. Increased PIIINP and decreased MMP-9 and TIMP-1 concentrations and decreased MMP-9:TIMP-1 ratios were found not only in KD patients with persistent CAL but also in KD patients without CAL, although to a lesser extent in the latter group. In KD patients, the concentrations of PIIINP were positively associated with the severity of coronary stenosis/occlusion (r = 0.72, P = 0.011) and with the extent of coronary thrombus (r = 0.64, P = 0.014). The concentrations of high-sensitivity C-reactive protein, however, did not differ across groups. Our results demonstrate alterations in extracellular matrix biomarkers in KD patients, suggesting enhanced collagen synthesis and ameliorated degradation in adolescents and young adults late after the onset of KD. We also observed an association between the concentrations of PIIINP and the extent of coronary stenosis/occlusion or thrombosis in KD patients, a finding that needs confirmation in further studies.