MMP-9 as a Biomarker for Predicting Hemorrhagic Strokes in Moyamoya Disease.

Junlin Lu,Yahui Zhao,Guangchao Shi,Jingyi Wang,Jizong Zhao,Rong Wang,Zhidong Lin,Yuanli Zhao

doi:10.3389/fneur.2021.721118

Abstract

Objective: This study was conducted in order to investigate the association of matrix metalloproteinase (MMP)-9 levels with phenotypes of moyamoya disease (MMD).Methods: This study included plasma samples from 84 MMD patients. The clinical variables of these patients were reviewed from the medical record. The serum concentration of tight junction, adherens junction proteins, and MMPs (MMP-2 and MMP-9) was determined using the ELISA method. Patients with hemorrhagic-onset MMD were compared with those with ischemic-onset MMD.Results: Compared with pediatric patients, the expression of MMP-9 was significantly higher, while the MMP-2 and vascular endothelial-cadherin were lower in adult patients. In adult subgroup analysis, hemorrhagic MMD patients exhibited significantly higher serum concentrations of MMP-9 compared with ischemic MMD patients. The ROC curve identified that a baseline serum MMP-9 level >1,011 ng/ml may be associated with spontaneous hemorrhage in adult MMD patients with 70.37% sensitivity and 71.88% specificity [area under curve (AUC), 0.73; 95% CI 0.597–0.864; P = 0.003]. A late Suzuki stage (>4) (OR 4.565, 95% CI 1.028–20.280, P = 0.046) and serum concentrations of MMP-9 >1,011 ng/ml (OR 7.218, 95% CI 1.826–28.533, P = 0.005) are risk predictors of hemorrhages in MMD patients. Hemorrhagic-type MMD patients had higher serum levels of MMP-9 and BBB permeability compared with ischemic-type MMD patients. Adult MMD patients had higher serum levels of MMP-9 and BBB permeability compared with pediatric patients.Conclusions: MMP-9 might serve as a biomarker for hemorrhage prediction in MMD. Serum MMP-9 level >1,011 ng/ml is an independent risk factor of MMD hemorrhagic strokes.

Highlights

Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterized by idiopathic progressive stenosis or occlusion at the terminal portion of the internal carotid artery [1, 2]
The Receiver operating characteristic (ROC) curve identified that a baseline serum Matrix metalloproteinases (MMPs)-9 level >1,011 ng/ml may be associated with spontaneous hemorrhage in adult moyamoya disease (MMD) patients with 70.37% sensitivity and 71.88% specificity [area under curve (AUC), 0.73; 95% CI 0.597–0.864; P = 0.003]
Hemorrhagic-type MMD patients had higher serum levels of MMP-9 and blood–brain barrier (BBB) permeability compared with ischemic-type MMD patients

Summary

Introduction

Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterized by idiopathic progressive stenosis or occlusion at the terminal portion of the internal carotid artery [1, 2]. The underlying pathophysiology leading to MMD phenotypes remains unclear. Matrix metalloproteinases (MMPs) are calcium-dependent zinc-endopeptidases of the metzincin superfamily which plays an important role in many physiological functions, including extracellular matrix tissue remodeling and immune response [8]. They have been recently proposed as possible biomarker in different neurological immune-mediated disorders [9,10,11]. A recent study indicated the involvement of MMP-9 in MMD pathophysiology [14], but whether the expression of MMP-9 contributes to different phenotypes of MMD has not been investigated yet

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Discussion

Conclusion