Relationship between MMP-9 serum levels and tHcy levels and total imaging load and cognitive dysfunction

Zhao, Jianhua; Li, Qiong; Meng, Lifang; Wang, Fan; Li, Qing; Yang, Fang; Wang, Minghua; Yu, Miao; Zhang, Jian; Li, Shaomin; Ji, Si-Bei

doi:10.1016/j.jstrokecerebrovasdis.2022.106759

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…They indicate that an increased MMP-9 level in the acute phase of ischemic stroke was associated with three-month cognitive impairment, independent of adopted risk factors; this is consistent with our present data indicating that the pre-rehabilitation level of MMP-9 gene expression was negatively correlated with an improvement in cognition ( Table 5 ) [ 56 ]. Interestingly, serum MMP-9 level has also been proposed as a significant factor for diagnosing cognitive impairment due to cerebral small vessel disease, which suggests that MMP-9 may be associated with vascular dementia [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Serum VEGF, IGF-1 and MMP-9 and Expression of Their Genes as Potential Prognostic Markers of Recovery in Post-Stroke Rehabilitation—A Prospective Observational Study

et al. 2023

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The key period in post-stroke recovery is the first three months due to the high activity of spontaneous and therapeutic-induced processes related to neuroplasticity, angiogenesis and reperfusion. Therefore, the present study examines the expression of VEGF, IGF-1 and MMP-9 proteins and their genes to identify biomarkers that can prognose brain repair ability and thus estimate the outcome of stroke. It also identifies possible associations with clinical scales, including cognitive assessment and depression scales. The study group comprised 32 patients with moderate ischemic stroke severity, three to four weeks after incident. The results obtained after three-week hospitalization indicate a statistically significant change in clinical parameter estimations, as well as in MMP9 and VEGF protein and mRNA expression, over the rehabilitation process. Our findings indicate that combined MMP9 protein and mRNA expression might be a useful biomarker for cognitive improvement in post-stroke patients, demonstrating 87% sensitivity and 71% specificity (p < 0.0001).

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Section: Discussionmentioning

confidence: 99%

Circulating Serum VEGF, IGF-1 and MMP-9 and Expression of Their Genes as Potential Prognostic Markers of Recovery in Post-Stroke Rehabilitation—A Prospective Observational Study

et al. 2023

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“…What is less clear, partly due to the obscuring effects of the relationship between CKD and cerebrovascular risk factors such as diabetes and hypertension, is why this is the case. Activation of MMPs within the neurovascular unit has been reported in several forms of cerebrovascular disease, including stroke 53 , traumatic injury 54 , cerebral small vessel disease 55 and, notably, in murine models of CKD 56 . By elaborating a mechanistic link between gut microbe/host co-derived pCS, cerebrovascular MMP activity and impaired BBB integrity, we provide an explanation for how cerebral vessels may be damaged in CKD.…”

Section: Discussionmentioning

confidence: 99%

Cerebrovascular damage caused by the gut microbe/host co-metabolitep-cresol sulfate is prevented by blockade of the EGF receptor

Shah

Knausenberger

Connell

et al. 2022

Preprint

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Chronic kidney disease is linked to impaired cognitive function and increased neurovascular disease risk even after correction for classical risk factors. The mechanism(s) underlying these links are unclear but may involve interactions of uraemic toxins with the blood-brain barrier (BBB). Here, we studied how the major uraemic toxinp-cresol sulfate (pCS) could affect BBB integrity. Exposure of human hCMEC/D3 endothelial cells to pCS dose-dependently increased paracellular permeability and disrupted intercellular tight junctions, a permeabilising effect mirrored in mice. Whole brain RNAseq analysis identified pCS-mediated suppression of neuronal activity, transcription and mitochondrial respiration pathways.In vitrostudies identified pCS binding to the epidermal growth factor receptor (EGFR), leadingviaannexin A1 and STAT3 signalling to mobilisation of matrix metalloproteinase (MMP)-2/9. Confirming this pathwayin vivo, the BBB damaging effects of pCS were prevented by pre-treatment with the EGFR antagonist erlotinib or the MMP2/9 inhibitor SB-3CT. Finally, hCMEC/D3 cells exposed to haemodialysis patient serum, but not to that of healthy donors, showed an erlotinib-sensitive increase in paracellular permeability that closely correlated in size to the total serum pCS content. Overall, we define a pathway linking the uraemic toxin pCS with BBB damage suggesting that targeting the EGFR may be useful in mitigating against cerebrovascular damage in chronic kidney disease.Translational StatementPatients with chronic kidney disease (CKD) have increased risk of cognitive impairment and stroke, pathologies associated cerebromicrovascular disease, but it is not clear why. Here, we show that the uraemic toxin p-cresol sulfate impairs BBB functionin vitroandin vivothrough EGFR-dependent MMP mobilisation. Importantly, serum from haemodialysis patients can also impair permeability of anin vitroBBB model, an effect prevented by EGFR inhibition, and proportional in magnitude to serum pCS content. Our data suggest that existing EGFR inhibitory drugs might have utility in preventing cerebral small vessel disease in CKD patients.

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“…The standard for smokers were those who smoke for 5 years with an average of 10 or more cigarettes per day; The standard for drinkers were those who drink for more than 5 years and ethanol intake of 30 g or more per day. [14] Hypertension and diabetes were diagnosed before admission or at the time of admission. The admission criteria were as below: met the diagnostic standard established by the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018 [15] ; relatively complete clinical data was available.…”

Section: Methodsmentioning

confidence: 99%

Neutrophil to high-density lipoprotein cholesterol ratio, a novel risk factor associated with acute ischemic stroke

Hao

et al. 2023

Medicine

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To investigate the relationship between neutrophil to high-density lipoprotein cholesterol ratio (NHR) and Acute Ischemic Stroke (AIS), and provide a new direction for the diagnosis and prevention of AIS. A total of 158 patients with AIS and 162 healthy individuals were recruited. Demographic, clinical, and laboratory data of participants were obtained and the multivariable logistic regression analysis was employed to assess risk factors for AIS. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic value of NHR for AIS. The spearman correlation analysis was used to estimate the correlation between NHR and national institute of health stroke scale (NIHSS) score. The age, White blood cell, MONO (monocyte), NEUT (neutrophil), creatinine, TG (triglyceride), NHR, neutrophil to lymphocyte ratio and MONO to high-density lipoprotein cholesterol ratio were remarkably greater and HDL-C (high-density lipoprotein cholesterol) was dramatically lower in the case group compared with in the control group (P < .05). The multivariable logistic regression analysis revealed that age [OR = 1.095, 95% CI (1.056, 1.135)], TG [OR = 6.188, 95% CI (2.900, 13.206)] and NHR [OR = 11.394, 95% CI (1.196, 108.585)] were independent risk factors for AIS (P < .05). The areas under the curve (AUCs) for the prediction of AIS by the age, TG and NHR were 0.694, 0.686, 0.782, respectively, the specificity were 56.8%, 88.3%, 87.0%, and the sensitivity were 75.3%, 44.3%, 56.3%, respectively (P < .05). In addition, spearman correlation analysis indicated that there was a positive correlation between NHR and NIHSS score (R = 0.558, P < .05). The level of NHR was higher in patients with a NIHSS score of above 5 points compared with those with a NIHSS score of 5 points or lower (P < .0001). The age, TG, and NHR were independent risk factors for AIS, and the level of NHR was positively correlated with severity of AIS.

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Relationship between MMP-9 serum levels and tHcy levels and total imaging load and cognitive dysfunction

Cited by 8 publications

References 19 publications

Circulating Serum VEGF, IGF-1 and MMP-9 and Expression of Their Genes as Potential Prognostic Markers of Recovery in Post-Stroke Rehabilitation—A Prospective Observational Study

Circulating Serum VEGF, IGF-1 and MMP-9 and Expression of Their Genes as Potential Prognostic Markers of Recovery in Post-Stroke Rehabilitation—A Prospective Observational Study

Cerebrovascular damage caused by the gut microbe/host co-metabolitep-cresol sulfate is prevented by blockade of the EGF receptor

Neutrophil to high-density lipoprotein cholesterol ratio, a novel risk factor associated with acute ischemic stroke

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