scholarly journals Variants in matrix metalloproteinase‐9 gene are associated with hemorrhagic transformation in acute ischemic stroke patients with atherothrombosis, small artery disease, and cardioembolic stroke

2019 ◽  
Vol 9 (6) ◽  
Author(s):  
Xingyang Yi ◽  
Guo Sui ◽  
Qiang Zhou ◽  
Chun Wang ◽  
Jing Lin ◽  
...  
2018 ◽  
Vol 6 (11) ◽  
pp. 2067-2072 ◽  
Author(s):  
Ismail Setyopranoto ◽  
Rusdy Ghazali Malueka ◽  
Andre Stefanus Panggabean ◽  
I Putu Eka Widyadharma ◽  
Ahmad Hamim Sadewa ◽  
...  

BACKGROUND: Hyperglycemia is common in acute stroke patients. Hyperglycemia can induce the production of reactive oxygen species, causing increased activity of matrix metalloproteinase-9 (MMP-9). AIM: This study aimed to determine an association between the increased levels of MMP-9 and the incidence of hyperglycemia in acute ischemic stroke patients. METHODS: This is a case-control study. Acute ischemic stroke patients admitted to the Stroke Unit of a reference hospital in Yogyakarta, Indonesia was divided into the hyperglycemic and non-hyperglycemic group. Demographic and clinical characteristics of each subject were recorded, and blood levels of MMP-9 were measured. Seventy-one patients were recruited, 40 subjects in the hyperglycemic group and 31 subjects in the non-hyperglycemic group. RESULTS: The median levels of blood MMP-9 level in the hyperglycemic and non-hyperglycemic group were 974.37 and 748.48 ng/mL, respectively, and the difference was statistically not significant (95% CI, 191.24-2849.53; p = 0.07). When the calculated cut-off point of 600.99 ng/mL was used, the proportion of patients with higher MMP-9 levels was significantly more in the hyperglycemic group compared with the ones in the non-hyperglycemic group (82.5% and 54.8%, respectively; OR = 3.88; p = 0.011). CONCLUSION: We concluded that the proportion of patients with MMP-9 level >600.99 ng/mL was significantly higher in acute ischemic stroke patients with hyperglycemia.ng/mL was significantly higher in acute ischemic stroke patients with hyperglycemia.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ly Pham ◽  
Sydney O’Connor ◽  
Karen Yarbrough ◽  
Sven Jacobson ◽  
Barney J Stern ◽  
...  

Background: Elevated matrix metalloproteinase-9 (MMP-9) following acute ischemic stroke is associated with blood-brain barrier breakdown and hemorrhagic conversion. Prior retrospective evidence suggests that sulfonylurea use may be associated with reduced risk of hemorrhagic conversion. We hypothesized that sulfonylureas may reduce MMP-9 level in stroke patients. Methods: Using serial plasma samples from six subjects in the Glyburide Advantage in Malignant Edema and Stroke Pilot trial (GAMES-Pilot), we evaluated the level of MMP-9 in human subjects presenting with large hemispheric stroke who were treated with intravenous glyburide (RP-1127). MMP-9 was measured in a control cohort with large ischemic stroke who were not treated with glyburide. Commercially available ELISA kits and gel zymography were used to measure MMP-9 at baseline and at approximately 48 hours after stroke. GAMES subjects had additional time points analyzed until approximately 84 hours after stroke. Results: Average MMP-9 level in glyburide-treated stroke patients was 47.2 ± 8.0 ng/mL compared to 143.4 ± 60.35 ng/mL in untreated control subjects (p=0.004). Zymography analysis demonstrated a significant decrease in the pro-enzyme but no change in the active form of MMP-9. There was no difference in the level of the MMP-9 specific inhibitor, TIMP-1. No subjects exhibited parenchymal hemorrhagic conversion on 24 hour head CT scan. Conclusions: Glyburide treatment in human stroke patients with large hemispheric stroke is associated reduced level of MMP-9. Elucidating the underlying mechanism of glyburide’s effect on MMP-9 and the risk of hemorrhagic conversion may highlight future directions of therapy, including in combination with intravenous tissue plasminogen activator (IV t-PA).


2020 ◽  
Vol 11 ◽  
Author(s):  
Lu Wang ◽  
Linghui Deng ◽  
Ruozhen Yuan ◽  
Junfeng Liu ◽  
Yuxiao Li ◽  
...  

Introduction: The role of matrix metalloproteinase 9 (MMP-9) and cellular fibronectin (c-Fn) in acute ischemic stroke is controversial. We systematically reviewed the literature to investigate the association of circulating MMP-9 and c-Fn levels and MMP-9 rs3918242 polymorphism with the risk of three outcome measures after stroke.Methods: We searched English and Chinese databases to identify eligible studies. Outcomes included severe brain edema, hemorrhagic transformation, and poor outcome (modified Rankin scale score ≥3). We estimated standardized mean differences (SMDs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs).Results: Totally, 28 studies involving 7,239 patients were included in the analysis of circulating MMP-9 and c-Fn levels. Meta-analysis indicated higher levels of MMP-9 in patients with severe brain edema (SMD, 0.76; 95% CI, 0.18–1.35; four studies, 419 patients) and hemorrhagic transformation (SMD, 1.00; 95% CI, 0.41–1.59; 11 studies, 1,709 patients) but not poor outcome (SMD, 0.30; 95% CI, −0.12 to 0.72; four studies, 759 patients). Circulating c-Fn levels were also significantly higher in patients with severe brain edema (SMD, 1.55; 95% CI, 1.18–1.93; four studies, 419 patients), hemorrhagic transformation (SMD, 1.75; 95% CI, 0.72–2.78; four studies, 458 patients), and poor outcome (SMD, 0.46; 95% CI, 0.16–0.76; two studies, 210 patients). Meta-analysis of three studies indicated that the MMP-9 rs3918242 polymorphism may be associated with hemorrhagic transformation susceptibility under the dominant model (TT + CT vs. CC: OR, 0.621; 95% CI, 0.424–0.908; P = 0.014). No studies reported the association between MMP-9 rs3918242 polymorphism and brain edema or functional outcome after acute stroke.Conclusion: Our meta-analysis showed that higher MMP-9 levels were seen in stroke patients with severe brain edema and hemorrhagic transformation but not poor outcome. Circulating c-Fn levels appear to be associated with all three outcomes including severe brain edema, hemorrhagic transformation, and poor functional outcome. The C-to-T transition at the MMP-9 rs3918242 gene appears to reduce the risk of hemorrhagic transformation.


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