SERPINA3: A novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke

作者全名："Hu, Xiao; Xiao, Zhong-Song; Shen, Yi-Qing; Yang, Wen-Song; Wang, Peng; Li, Pei-Zheng; Wang, Zi-Jie; Pu, Ming-Jun; Zhao, Li-Bo; Xie, Peng; Li, Qi"

作者地址："[Hu, Xiao; Xiao, Zhong-Song; Shen, Yi-Qing; Yang, Wen-Song; Wang, Peng; Li, Pei-Zheng; Wang, Zi-Jie; Pu, Ming-Jun; Xie, Peng; Li, Qi] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Xiao, Zhong-Song; Shen, Yi-Qing; Yang, Wen-Song; Wang, Peng; Li, Pei-Zheng; Xie, Peng; Li, Qi] Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing, Peoples R China; [Wang, Zi-Jie; Li, Qi] Anhui Med Univ, Dept Neurol, Hosp 2, 678 Furong Rd, Hefei 230601, Peoples R China; [Zhao, Li-Bo] Chongqing Med Univ, Dept Neurol, Yongchuan Hosp, Chongqing, Peoples R China; [Zhao, Li-Bo] Chongqing Key Lab Cerebrovasc Dis Res, Chongqing, Peoples R China"

通信作者："Xie, P; Li, Q (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China.; Li, Q (通讯作者)，Anhui Med Univ, Dept Neurol, Hosp 2, 678 Furong Rd, Hefei 230601, Peoples R China."

来源：CNS NEUROSCIENCE & THERAPEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001068421100001

JCR分区：Q1

影响因子：4.8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：cerebral small vessel disease; inflammation; SERPINA3; white matter hyperintensity

摘要："Background and Objective: Inflammation has emerged as a prominent risk factor for cerebral small vessel disease (CSVD). However, the specific association between various inflammatory biomarkers and the development of CSVD remains unclear. Serine proteinase inhibitor A3 (SERPINA3), Matrix metalloproteinase-9 (MMP-9), Tissue inhibitor metalloproteinase-1 ( TIMP-1), Monocyte Chemoattractant Protein-1 (MCP-1) are several inflammatory biomarkers that are potentially involved in the development of CSVD. In this present study, we aimed to investigate the relationship between candidate molecules and CSVD features. Method: The concentration of each biomarker was measured in 79 acute ischemic stroke patients admitted within 72 h after symptom onset. The associations between blood levels of inflammatory markers and CSVD score were investigated, as well as each CSVD feature, including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (EPVS). Results: The mean age was 69.0 +/- 11.8 years, and 65.8% of participants were male. Higher SERPINA3 level (>78.90 ng/mL) was significantly associated with larger WMH volume and higher scores on Fazekas's scale in all three models. Multiple regression analyses revealed the linear association between absolute WMH burden and SERPINA3 level, especially in model 3 (ss = 0.14; 95% confidence interval [CI], 0.04-0.24; p = 0.008). Restricted cubic spline regression demonstrated a dose-response relationship between SERPINA3 level and larger WMH volume (p nonlineariy = 0.0366 and 0.0378 in model 2 and mode 3, respectively). Using a receiving operating characteristic (ROC) curve, plasma SERPINA3 level of 64.15 ng/mL distinguished WMH >7.8 mL with the highest sensitivity and specificity (75.92% and 60%, respectively, area under curve [AUC] = 0.668, p = 0.0102). No statistically significant relationship has been found between other candidate biomarkers and CSVD features. Conclusion: In summary, among four inflammatory biomarkers that we investigated, SERPINA3 level at baseline was associated with WMH severity, which revealed a novel biomarker for CSVD and validated its relationship with inflammation and endothelial dysfunction."

基金机构："We thank all the participants, their relatives, and the members of this research team."

基金资助正文："We thank all the participants, their relatives, and the members of this research team."