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

Abstract

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.

circSKA3 acts as a sponge of miR‐6796‐5p to be associated with outcomes of ischemic stroke by regulating matrix metalloproteinase 9 expression

“…MMP9 is the most investigated member of the matrix metalloproteinase family, which normally remodels the extracellular matrix and pathologically attacks substrates as part of the neuroinflammatory response. Previous studies from the China Antihypertensive Trial in Acute Ischemic Stroke reported a positive association of baseline MMP9 levels with the risk of poor functional outcome, poststroke cognitive impairment, and depression [10–12]. On the other hand, MMP9 was demonstrated to be regulated by some long noncoding RNAs through the ceRNA network [16], which was similar with our findings.…”

“…circRNAs were demonstrated to be involved in the progression of ischemic stroke through the ceRNA network of circRNA-miRNA-mRNA. For instance, circDLGAP4 functioned as an endogenous miRNA-143 sponge to inhibit miRNA-143 activity, resulting in the inhibition of homologous to the E6-AP C-terminal domain E3 ubiquitin [10][11][12]. On the other hand, MMP9 was demonstrated to be regulated by some long noncoding RNAs through the ceRNA network [16], which was similar with our findings.…”

“…Matrix metalloproteinase 9 (MMP9) is the most widely investigated enzyme in acute ischemic stroke, and its expression is rapidly upregulated after cerebral ischemia [9]. Several clinical studies have reported the association between MMP9 and the prognosis of ischemic stroke [10][11][12]. In the present study, we aim to construct and verify the ceRNA network of circRNA-miRNA-MMP9 based on high-throughput sequencing, quantitative polymerase chain reaction (PCR) validation, and luciferase reporter assay.…”

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

“…In a population of about 600 ischemic stroke patients and in a period of 3 months after the event, approximately 40% of the patient population were classified to have post-stroke depression symptoms, and the MMP-9 level in these patients (658.8 ng/mL on average) were much higher than those identified without post-stroke depression (485.7 ng/mL on average) [143]. Patients' blood samples were collected after a minimum of 8 h of fasting for MMP-9 measurements; MMP-9 serum was detected and measured using commercially available ELISA kits [143]. It was suggested that MMP-9 was also involved in cerebral damage following stroke events [143].…”

“…Patients' blood samples were collected after a minimum of 8 h of fasting for MMP-9 measurements; MMP-9 serum was detected and measured using commercially available ELISA kits [143]. It was suggested that MMP-9 was also involved in cerebral damage following stroke events [143].…”