Serum matrix metalloproteinase-9 levels and prognosis of acute ischemic stroke

Zhong, Chongke; Yang, Jingyuan; Xu, Tan; Xu, Tian; Peng, Yi; Wang, Aili; Wang, Jinchao; Peng, Hao; Li, Qunwei; Ju, Zhong; Geng, Deqin; Zhang, Yonghong; He, Jiang

doi:10.1212/wnl.0000000000004257

Cited by 111 publications

(74 citation statements)

References 33 publications

(38 reference statements)

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“…31 Our previous studies found that elevated MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of death, major disability, and cognitive impairment. 32,33 These findings could be preliminary evidence for MMP-9's predictive effect on poor prognosis of ischemic stroke.…”

Section: Discussionmentioning

confidence: 67%

Serum Matrix Metalloproteinase-9 Is Associated With Depression After Acute Ischemic Stroke

Che

Zhong

et al. 2019

Circ J

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Background: Matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, might cause cerebral damage after stroke and be involved in the development of depressive symptoms. This study aimed to evaluate the association of serum MMP-9 levels and post-stroke depression (PSD). Methods and Results: Serum MMP-9 levels were determined in 558 acute ischemic stroke patients from 7 hospitals comprising the China Antihypertensive Trial in Acute Ischemic Stroke. We assessed depression status using the 24-item Hamilton Depression Rating Scale and defined PSD as a cutoff score of 8. Logistic regression was performed to estimate the risk of PSD associated with serum MMP-9. Discrimination and reclassification for PSD by MMP-9 were analyzed. A total of 222 (39.8%) stroke patients were categorized as PSD within 3 months. Serum MMP-9 concentrations were higher among PSD patients than those without PSD (658.8 vs. 485.7 ng/mL; P<0.001). The multiple-adjusted odds ratio (95% confidence interval) for the highest MMP-9 quartile compared with the lowest quartile was 4.36 (2.49-7.65) for PSD, and 1 standard deviation higher log-MMP-9 was associated with 68% (37-106%) increased odds of PSD. Adding MMP-9 to the conventional risk factors model substantially improved discrimination and reclassification for PSD (all P<0.05). Conclusions: Elevated serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of PSD, suggesting an important prognostic role of MMP-9 for PSD.

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Section: Discussionmentioning

confidence: 67%

Serum Matrix Metalloproteinase-9 Is Associated With Depression After Acute Ischemic Stroke

Che

Zhong

et al. 2019

Circ J

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“…Experimental studies showed that the expression of circulating MMP-9 is rapidly upregulated after cerebral ischemia, 7 and our previous study found higher serum MMP-9 levels in the short-term phase of ischemic stroke were associated with increased risk of mortality and major disability. 26 However, limited studies have investigated the relationship between serum MMP-9 and cognitive impairment, especially in patients with acute ischemic stroke. 12,13,27 A case-control study of 15 patients with vascular dementia and 8 neurologically normal controls showed that MMP-9 levels were significantly elevated in the cerebrospinal fluid in the cases compared with controls.…”

Section: Discussionmentioning

confidence: 99%

“…Median (interquartile range) scores of MMSE and MoCA were 26 (22)(23)(24)(25)(26)(27)(28)(29) and 22 (18)(19)(20)(21)(22)(23)(24)(25)(26), respectively. After adjustment for age, sex, education level, admission NIHSS score, and other Figure 2).…”

Section: Association Between Serum Mmp-9 and Cognitive Impairmentmentioning

confidence: 99%

Serum Matrix Metalloproteinase‐9 and Cognitive Impairment After Acute Ischemic Stroke

Zhong

et al. 2018

JAHA

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BackgroundThe impact of serum matrix metalloproteinases‐9 (MMP‐9) on cognitive impairment after ischemic stroke is unclear. We aimed to investigate the association between serum MMP‐9 in the short‐term acute phase of ischemic stroke and cognitive impairment at 3 months.Methods and ResultsOur study was based on a subsample from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke); a total of 558 patients with serum MMP‐9 levels from 7 of 26 participating sites of the trial were included in this analysis. Cognitive impairment severity was categorized as severe, mild, or none (Mini‐Mental State Examination score, <23, 23–26, or ≥27, respectively; Montreal Cognitive Assessment score, <20, 20–24, or ≥25, respectively). Cognitive impairment was defined as a score of <27 for Mini‐Mental State Examination or <25 for Montreal Cognitive Assessment. According to Mini‐Mental State Examination score, 143 participants (25.6%) had mild cognitive impairment and 153 (27.4%) had severe cognitive impairment at 3 months. After adjustment for age, National Institutes of Health stroke score, education, and other covariates, the odds ratio for the highest quartile of serum MMP‐9 compared with the lowest quartile was 3.20 (95% confidence interval, 1.87–5.49) for cognitive impairment. Multiple‐adjusted spline regression model showed a linear association between MMP‐9 levels and cognitive impairment (P<0.001 for linearity). Sensitivity and subgroup analyses further confirmed these results. Similar significant findings were observed when cognitive impairment was defined by Montreal Cognitive Assessment score.ConclusionsIncreased serum MMP‐9 levels in the short‐term phase of ischemic stroke were associated with 3‐month cognitive impairment, independently of established risk factors.

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“…The upregulation of MMP9 was revealed to be involved in the development and progression of a number of vascular diseases [13,36,42]. The -1562C/T polymorphism in the promoter region of the MMP9 gene abolishes the DNA-protein interaction, resulting in higher activity of the T-allelic promoter [14].…”

Section: Discussionmentioning

confidence: 99%

Association of Polymorphisms of the Matrix Metalloproteinase 9 Gene with Ischaemic Stroke in a Southern Chinese Population

Li¹,

Chen²,

Yao³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Matrix metalloproteinase 9 (MMP9), a potent endopeptidase degrading extracellular matrix, plays a pivotal role in the pathogenesis of ischaemic stroke (IS). The present study was undertaken to determine the association of MMP9 gene polymorphisms and the risk of IS in a southern Chinese population. Methods: A cohort of 1274 patients and 1258 age-matched healthy controls were genotyped to detect the four MMP9 polymorphisms (rs17156, rs3787268, rs3918241 and rs3918242) using SNaPshot. Results: Our study demonstrated a significant difference in the genotype and allele frequencies of the MMP9 rs3918242 polymorphism between the IS patients and the controls (P = 0.012 for the genotype and P = 0.0092 for the allele). Stratification by smoking status showed statistically significant differences in the frequency and allele of the rs3918242 polymorphism between IS patients and the controls (P = 0.0052 for the genotype and P = 0.0019 for the allele). Further stratification by IS subtypes revealed that the presence of the T allele of the MMP9 rs3918242 polymorphism confers a higher risk of the large artery atherosclerosis subtype of IS (P = 0.017). Moreover, IS patients with the rs3918242 T allele of MMP9 presented with increased serum MMP9 production, and this increase was more significant in smokers with IS (P = 0.022). Patients carrying the variant T allele of the MMP9 rs3918242 polymorphism exhibited significantly higher infarct volumes than those with the major CC genotype (P = 0.036). Conclusion: Our study provides preliminary evidence that the MMP9 rs3918242 polymorphism is linked to a higher risk of IS, confirming the role of MMP9 in the pathophysiology of IS, with potentially important therapeutic implications.

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Serum matrix metalloproteinase-9 levels and prognosis of acute ischemic stroke

Abstract: Higher serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of mortality and major disability, suggesting that serum MMP-9 could be an important prognostic factor for ischemic stroke.

Cited by 111 publications

References 33 publications

Serum Matrix Metalloproteinase-9 Is Associated With Depression After Acute Ischemic Stroke

Serum Matrix Metalloproteinase-9 Is Associated With Depression After Acute Ischemic Stroke

Serum Matrix Metalloproteinase‐9 and Cognitive Impairment After Acute Ischemic Stroke

Association of Polymorphisms of the Matrix Metalloproteinase 9 Gene with Ischaemic Stroke in a Southern Chinese Population

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