The Graduate School of Fujian Medical University, Fuzhou 350000, China; Department of Neurology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen 361000, Fujian, China.
Department of Neurology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen 361000, Fujian, China.
Magn Reson Imaging. 2024 Nov;113:110213. doi: 10.1016/j.mri.2024.110213. Epub 2024 Jul 23.
The objective of this study was to investigate the correlation between serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels and their ratios with the severity of white matter hyperintensities (WMHs) in patients with cerebral small vessel disease (CSVD).
This cross-sectional study was done on a prospective cohort of patients with CSVD. Qualitative and quantitative analyses of WMHs were performed using Fazekas grading and lesion prediction algorithm (LPA) methods. Biomarkers MMP-2, MMP-9, and TIMP-1 were measured to explore their correlation with the severity of WMHs.
The sample consisted of 144 patients with CSVD. There were 63 male and 81 female patients, with an average age of 67.604 ± 8.727 years. Among these, 58.33% presented with white matter hyperintensities at Fazekas grading level 1, with an average total template volume of WMHs of 4.305 mL. MMP-2 (P = 0.025), MMP-9 (P = 0.008), TIMP-1 (P = 0.026), and age (P = 0.007) were identified as independent correlates of WMHs based on Fazekas grading. Independent correlates of the total template volume of WMHs included MMP-2 (P = 0.023), TIMP-1 (P = 0.046), age (P = 0.047), systolic blood pressure (P = 0.047), and homocysteine (Hcy) (P = 0.014). In addition, age (P = 0.003; P < 0.001), interleukin-6 (IL-6) (P < 0.001; P = 0.044), Hcy (P < 0.001; P < 0.001), glycated hemoglobin (HbA1c) (P = 0.016; P = 0.043), and chronic kidney disease (P < 0.001; P < 0.001) were associated with both WMHs Fazekas grading and the total template volume of WMHs.
Serum levels of MMP-9, MMP-2, and TIMP-1 were independently associated with the Fazekas grading, while serum TIMP-1 and MMP-2 levels were independently related to the total template volume of WMHs. The association of TIMP-1 and MMP-2 with the severity of CSVD-related WMHs suggests their potential role as disease-related biomarkers. However, further research is required to uncover the specific mechanisms underlying these interactions.
本研究旨在探讨血清基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶组织抑制剂-1（TIMP-1）水平及其比值与脑小血管病（CSVD）患者脑白质高信号（WMHs）严重程度的相关性。
本研究为前瞻性队列研究，纳入 CSVD 患者。采用 Fazekas 分级和病变预测算法（LPA）方法对 WMHs 进行定性和定量分析。测定 MMP-2、MMP-9 和 TIMP-1 等生物标志物，以探讨其与 WMHs 严重程度的相关性。
本研究共纳入 144 例 CSVD 患者，其中男性 63 例，女性 81 例，平均年龄 67.604±8.727 岁。58.33%的患者 Fazekas 分级为 1 级脑白质高信号，总模板体积平均为 4.305mL。Fazekas 分级显示 MMP-2（P=0.025）、MMP-9（P=0.008）、TIMP-1（P=0.026）和年龄（P=0.007）是 WMHs 的独立相关因素。WMHs 总模板体积的独立相关因素包括 MMP-2（P=0.023）、TIMP-1（P=0.046）、年龄（P=0.047）、收缩压（P=0.047）和同型半胱氨酸（Hcy）（P=0.014）。此外，年龄（P=0.003；P＜0.001）、白细胞介素-6（IL-6）（P＜0.001；P=0.044）、Hcy（P＜0.001；P＜0.001）、糖化血红蛋白（HbA1c）（P=0.016；P=0.043）和慢性肾脏病（P＜0.001；P＜0.001）与 WMHs 的 Fazekas 分级和总模板体积均相关。
血清 MMP-9、MMP-2 和 TIMP-1 水平与 Fazekas 分级独立相关，而血清 TIMP-1 和 MMP-2 水平与 WMHs 总模板体积独立相关。TIMP-1 和 MMP-2 与 CSVD 相关 WMHs 严重程度相关，提示它们可能作为疾病相关生物标志物。然而，需要进一步研究以揭示这些相互作用的具体机制。
