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ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neurological Biomarkers
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1552948
NINJ1 and MMP9: Potential Biomarkers for Intracranial Atherosclerosis Plaque Instability
Provisionally accepted- The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
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Background and objective: To utilize high-resolution vessel wall imaging (HR-VWI) to identify the characteristic features of culprit plaques in intracranial atherosclerotic stenosis (ICAS) vessels and evaluate the predictive value of serum nerve injury-induced protein 1 (NINJ1) and matrix metalloproteinase 9 (MMP9) for the vulnerability of intracranial atherosclerotic plaques.This study included symptomatic intracranial atherosclerotic stenosis (sICAS) patients who underwent high-resolution vessel wall imaging (HR-VWI) and healthy individuals. Patients were divided into non-enhancement/enhancement, moderate/severe stenosis, and positive/negative remodeling groups. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate the predictive value of NINJ1 and MMP9 for plaque enhancement, severe stenosis, and positive remodeling.Results: NINJ1 and MMP9 levels were higher in the plaque enhancement group compared to the non-enhancement group (107.04 vs. 93.49, p = 0.001; 245.35 vs. 227.16, p = 0.002) and were independent risk factors for plaque enhancement (OR: 1.036, p = 0.003; OR: 1.022, p = 0.008). The area under the curve (AUC) for predicting plaque enhancement by NINJ1 and MMP9 were 0.676 and 0.667, respectively, and the combined AUC was 0.740. In the severe stenosis group, NINJ1 and MMP9 levels were also higher than in the moderate stenosis group (106.28 vs. 94.54, p = 0.006; 243.88 vs. 229.38, p = 0.014), with both being independent risk factors (OR: 1.027, p = 0.012; OR: 1.017, p = 0.027). The AUC for predicting severe stenosis by NINJ1 and MMP9 were 0.652 and 0.646, respectively, and the combined AUC was 0.686. For the positive remodeling group, NINJ1 and MMP9 levels were significantly elevated (108.73 vs. 97.27, p = 0.007; 248.36 vs. 230.42, p = 0.002), and both were independent risk factors (OR: 1.026, p = 0.015; OR: 1.023, p = 0.004). The AUC for predicting positive remodeling by NINJ1 and MMP9 were 0.642 and 0.672, respectively, and the combined AUC was 0.722.NINJ1 and MMP9 can serve as independent predictors factors for intracranial atherosclerotic plaque enhancement, severe stenosis, and positive remodeling. NINJ1 and MMP9 have the potential to be serum biomarkers for the vulnerability of intracranial atherosclerotic plaques.
Keywords: Nerve Injury-Induced Protein 1 (NINJ1), Matrix metalloproteinase 9 (MMP9), high-resolution vessel wall imaging (HR-VWI), symptomatic Intracranial Atherosclerotic Stenosis (sICAS), Plaque
Received: 29 Dec 2024; Accepted: 14 Apr 2025.
Copyright: © 2025 Wei, Da, Zhang, Li, Liu, Yan, Zhong and Yuan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bin Yuan, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
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