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MMP-9 as a Biomarker for Predicting Hemorrhagic Strokes in Moyamoya Disease
Junlin Lu1, Jingyi Wang2, Zhidong Lin3
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
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.
Insights
Matrix metalloproteinase (MMP)-9 levels are associated with moyamoya disease (MMD) phenotypes. Higher MMP-9 indicates increased risk of hemorrhagic strokes in adult MMD patients, suggesting its potential as a predictive biomarker.
Area of Science:
- Neuroscience
- Biochemistry
- Vascular Biology
Background:
- Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive stenosis of the internal carotid arteries.
- Understanding the molecular mechanisms underlying MMD phenotypes, particularly hemorrhagic versus ischemic onset, is crucial for risk stratification and management.
- Matrix metalloproteinases (MMPs), enzymes involved in extracellular matrix degradation, have been implicated in vascular remodeling and disease pathogenesis.
Purpose of the Study:
- To investigate the association between matrix metalloproteinase (MMP)-9 levels and distinct phenotypes of moyamoya disease (MMD).
- To identify potential biomarkers for predicting hemorrhagic complications in MMD patients.
- To compare MMP levels and blood-brain barrier (BBB) permeability between adult and pediatric MMD patients, and between hemorrhagic and ischemic MMD subtypes.
Main Methods:
- Plasma samples from 84 MMD patients were analyzed for serum concentrations of MMP-2 and MMP-9 using ELISA.
- Clinical data, including onset type (hemorrhagic vs. ischemic) and Suzuki stage, were reviewed.
- Comparisons were made between adult and pediatric MMD patients, and between hemorrhagic and ischemic MMD subgroups.
Main Results:
- Adult MMD patients exhibited significantly higher MMP-9 expression compared to pediatric patients.
- Hemorrhagic-onset MMD patients, particularly adults, showed significantly higher serum MMP-9 concentrations than ischemic-onset patients.
- A serum MMP-9 level >1,011 ng/ml was identified as a potential biomarker for spontaneous hemorrhage in adult MMD, with 70.37% sensitivity and 71.88% specificity (AUC, 0.73).
Conclusions:
- Elevated serum MMP-9 levels are associated with hemorrhagic phenotypes in moyamoya disease.
- Serum MMP-9 may serve as a valuable biomarker for predicting the risk of hemorrhage in MMD patients.
- A serum MMP-9 level exceeding 1,011 ng/ml is an independent risk factor for MMD hemorrhagic strokes in adults.
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