PMID- 37721405 OWN - NLM STAT- MEDLINE DCOM- 20240307 LR - 20240418 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 30 IP - 3 DP - 2024 Mar TI - SERPINA3: A novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke. PG - e14472 LID - 10.1111/cns.14472 [doi] LID - e14472 AB - 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 (beta = 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. CI - (c) 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. FAU - Hu, Xiao AU - Hu X AUID- ORCID: 0000-0002-1295-3293 AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Xiao, Zhong-Song AU - Xiao ZS AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Shen, Yi-Qing AU - Shen YQ AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Yang, Wen-Song AU - Yang WS AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Wang, Peng AU - Wang P AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Li, Pei-Zheng AU - Li PZ AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Wang, Zi-Jie AU - Wang ZJ AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - Department of Neurology, The Second Hospital of Anhui Medical University, Hefei, China. FAU - Pu, Ming-Jun AU - Pu MJ AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Zhao, Li-Bo AU - Zhao LB AD - Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, China. FAU - Xie, Peng AU - Xie P AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Li, Qi AU - Li Q AUID- ORCID: 0000-0002-9144-148X AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - Department of Neurology, The Second Hospital of Anhui Medical University, Hefei, China. LA - eng GR - National Natural Science Foundation of China (No. 82071337)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230918 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - 0 (Serine Proteinase Inhibitors) RN - 0 (Biomarkers) RN - 0 (SERPINA3 protein, human) RN - 0 (Serpins) SB - IM MH - Humans MH - Male MH - Middle Aged MH - Aged MH - Aged, 80 and over MH - Female MH - *Ischemic Stroke/complications MH - Magnetic Resonance Imaging MH - Serine Proteinase Inhibitors MH - *Cerebral Small Vessel Diseases/complications/diagnostic imaging MH - Biomarkers MH - Inflammation/diagnostic imaging/complications MH - *Serpins PMC - PMC10916418 OTO - NOTNLM OT - SERPINA3 OT - cerebral small vessel disease OT - inflammation OT - white matter hyperintensity COIS- The authors have no conflicts of interest to disclose. EDAT- 2023/09/18 12:44 MHDA- 2024/03/07 06:43 PMCR- 2023/09/18 CRDT- 2023/09/18 08:22 PHST- 2023/08/16 00:00 [revised] PHST- 2023/07/08 00:00 [received] PHST- 2023/09/04 00:00 [accepted] PHST- 2024/03/07 06:43 [medline] PHST- 2023/09/18 12:44 [pubmed] PHST- 2023/09/18 08:22 [entrez] PHST- 2023/09/18 00:00 [pmc-release] AID - CNS14472 [pii] AID - 10.1111/cns.14472 [doi] PST - ppublish SO - CNS Neurosci Ther. 2024 Mar;30(3):e14472. doi: 10.1111/cns.14472. Epub 2023 Sep 18.