Correlation Between Matrix Metalloproteinases With Coronary Artery Lesion Caused by Kawasaki Disease.

Fang Tian,Lijuan Ji,Linxi Ma,Renbing Zhao,Yu Jiang,Xiufen Wang,Wenli Sun

doi:10.3389/fped.2022.802217

Abstract

This study was designed to clarify the role of matrix metalloproteinases (MMPs) in coronary artery lesions (CAL). Serum samples were acquired from healthy, febrile, and Kawasaki disease (KD) children with or without CAL. Standard blood parameters were examined and enzyme-linked immunosorbent assay (ELISA) was used to assess the levels of MMP-2 and MMP-9. Intravenous immunoglobulin (IVIG) therapy was conducted on the KD patients and the changes of MMPs before and after treatment were compared. The correlations between MMP levels and clinical parameters were also evaluated. Compared to febrile and healthy controls, KD patients demonstrated clinical signs characteristic of abnormal immunoregulation. However, the clinical parameters of KD patients with or without CAL were not significantly different. MMP-2 and MMP-9 levels, however, were significantly higher in KD patients with CAL than those without CAL. IVIG treatment effectively downregulated the levels of MMPs in KD patients, which was more prominent in those with CAL. Significant correlations were found between MMP levels and some clinical parameters of KD, such as fever time, white blood cell count, etc. The upregulation of MMPs significantly correlates with coronary artery aneurysms (CAAs) in KD patients, making it important biomarkers of CAL in KD patients.

Highlights

Kawasaki disease (KD), known as cutaneous mucosal lymph node syndrome, is a systemic vasculitis syndrome caused by an autoimmune disorder [1]
We found that fever time, white blood cell count (WBC), red blood cell count (RBC), hemoglobin, platelet and PCT levels were not significantly different between the two groups but the levels of c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6 and monocyte chemoattractant protein-1 (MCP-1) of those with coronary artery lesions (CAL) were markedly higher than those without CAL (p = 0.017, 0.037, 0.007, and 0.012, respectively, Table 2)
Our study differs from the study by Korematsu et al in that we further explored the roles of more Matrix metalloproteinases (MMPs) and explored the correlation between MMP levels and clinical parameters of KD patients

Summary

Introduction

Kawasaki disease (KD), known as cutaneous mucosal lymph node syndrome, is a systemic vasculitis syndrome caused by an autoimmune disorder [1]. KD is characterized by activation of the immune system and extensive damage to the endothelial system [2]. During the acute phase of KD, the pronounced activation of immune system results in production of inflammatory mediators and proteases, as well as reactive oxygen species, which are believed to induce lesions in the vascular systems [3]. Infants and young children with KD are extremely vulnerable to coronary artery lesions (CALs), including myocardial infarctions, coronary artery fistula formations, coronary artery dilatations, and coronary artery aneurysms (CAAs). Despite progresses in clinical management of KD, 20% of children with KD progress to CAL and have a high mortality rate [4]. Matrix metalloproteinases (MMPs) are a family of enzymes responsible for degradation of extracellular matrix (ECM). The link of overexpression of specific MMPs and a number of human

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