Elevated serum levels of matrix metalloproteinase-9 (MMP-9) in Kawasaki disease

Abstract

SUMMARYMatrix metalloproteinases (MMPs) play an important role in the progression of tumour cells and the invasion of inflammatory cells by degrading the extracellular matrix. In the MMP family, MMP-9 gelatinase is thought to contribute to the pathogenesis of inflammatory arteritis by disrupting the elastic lamina. The aim of the present study is to investigate the potential role of MMP-9 in Kawasaki disease (KD), an acute type of systemic vasculitis in children. We studied the total levels of MMP-9 (free proMMP-9 and free MMP-9) in the sera using a new assay system and the expression of MMP-9 mRNA in the leucocytes using reverse transcription-polymerase chain reaction in 18 patients with KD, 10 patients with sepsis and 10 healthy children (HC). The serum MMP-9 levels were significantly higher (P , 0´01) in the acute phase of KD than in the acute phase of sepsis and HC. In the time course of KD, the serum MMP-9 levels decreased significantly (P , 0´01) from the subacute through the convalescent phases. In the acute phase of KD, the serum MMP-9 levels showed a significantly positive correlation (P , 0´05) with the circulating leucocyte counts, especially the neutrophil counts. Furthermore, the expression of MMP-9 mRNA in the circulating leucocytes increased in the acute phase of KD and decreased from the subacute through the convalescent phases. These findings indicate that an excessive amount of MMP-9 is present in the plasma during the acute phase of KD, thus suggesting that circulating leucocytes may be a source of the MMP-9 secreted into the circulation.

Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease

“…But despite the fact that MMP-9 levels were elevated in affected hearts in our murine model of KD, there was no correlation between circulating MMP-9 levels and enzymatic activity in affected coronary arteries (25). This is in accordance with data from cases of fatal KD, which show MMP-9 expression specifically localized to the site of coronary artery lesions (26), and the conflicting reports regarding circulating MMP-9 levels in affected children (22)(23)(24)(25). Degradation of elastin is one of the hallmarks of aneurysm formation.…”

“…MMP-9 may have a role in coronary artery aneurysm formation in KD. Despite conflicting data on serum levels of MMP-9 during the acute phase of KD (22)(23)(24)(25), local MMP-9 expression at the site of coronary artery aneurysms in children with KD has been documented (26). Circulating levels of molecules known to act locally may not be useful biomarkers of disease; this is especially relevant to enzymatic activity, which is tightly regulated at multiple levels including the local tissue environment (25).…”

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Statement for Health Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association

“…44 Enzymes including matrix metalloproteinases that are capable of damaging arterial wall integrity may be important in the development of aneurysmal dilatation. 46 Vascular endothelial growth factor (VEGF), monocyte chemotactic and activating factor (MCAF or MCP-1), tumor necrosis actor-␣ (TNF-␣), and various interleukins also appear to play important roles in the vasculitic process. [47][48][49][50][51][52][53][54] …”

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease

“…44 Enzymes including matrix metalloproteinases that are capable of damaging arterial wall integrity may be important in the development of aneurysmal dilatation. 46 Vascular endothelial growth factor (VEGF), monocyte chemotactic and activating factor (MCAF or MCP-1), tumor necrosis factor-␣ (TNF-␣), and various interleukins also appear to play important roles in the vasculitic process. [47][48][49][50][51][52][53][54] …”