Plasma let-7i and miR-15a expression are associated with the effect of recombinant tissue plasminogen activator treatment in acute ischemic stroke patients

Xiang, Wei; Tian, Canhui; Lin, Jianzhong; Wu, Xiaohui; Pang, Guanlai; Zhou, Liang; Pan, Suyue; Deng, Zhen

doi:10.1016/j.thromres.2017.09.004

Cited by 18 publications

(24 citation statements)

References 22 publications

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“…In addition, alteplase treatment may change the expression of certain miRNAs. 27,28 This study has several limitations. First, although our results were significant, our sample size was relatively small.…”

Section: Discussionmentioning

confidence: 96%

“…22,26 Nevertheless, it has also been confirmed that a variety of miRNA expression is altered after thrombolysis treatment, whether in intracranial or extracranial. 27,28 Thus, whether these alternative miRNAs can also be used as independent predictors after recanalization has not been fully addressed. In addition, in view of the presence of cerebral I/R injury after recanalization, I/R injury-related miRNAs in circulation might be associated with AIS.…”

Section: Discussionmentioning

confidence: 99%

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Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study

Shi

Zhao

et al. 2019

Journal of Stroke and Cerebrovascular Diseases

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Introduction: Multiple microRNAs (miRNAs) participate in the response to hypoxic/ ischemic and ischemia-reperfusion events. However, the expression of these miRNAs in circulation from patients with acute ischemic stroke (AIS) receiving recanalization treatment has not been examined, and whether they are associated with the severity and outcome of stroke is still unknown. Materials and methods: In this prospective cohort study, plasma levels of miR-125b-5p, miR-15a-3p, miR-15a-5p, and miR-206 were measured at 24 hours after thrombolysis with or without endovascular treatment in 94 patients with AIS, as determined by qRT-PCR. Stroke severity was assessed based on National Institutes of Health Stroke Scale (NIHSS) score and infarct lesion. Intracranial haemorrhage (ICH) was recorded. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2 at day 90 after stroke. Results: miR-125b-5p and miR-206 levels were correlated with NIHSS scores (P = .014 and P = .002) and cerebral infarction volumes (P = .025 and P = .030). miR-125b-5p levels were significantly higher in patients with an unfavorable outcome than in patients with a favorable outcome (P = .002) and showed good diagnostic accuracy in discriminating the presence of an unfavorable outcome (area under the curve .735, 95% confidence interval .623-.829, P < .001). No association was found between different miRNAs and ICH. Conclusions: In AIS patients after thrombolysis with or without endovascular treatment, miR-125b-5p is a novel prognostic biomarker highly associated with an unfavorable outcome. miR-125b-5p and miR-206 levels are associated with stroke severity.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study

Shi

Zhao

et al. 2019

Journal of Stroke and Cerebrovascular Diseases

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“…The let‐7 family are the first known human microRNAs to act as positive regulators of differentiation 16 . Our previous study, 17 along with other researches, 18‐23 have shown that circulating let‐7i and other numbers of let‐7 numbers are associated with ischemic stroke. Furthermore, our research concluded that circulating let‐7i is associated with the effect of recombinant tissue plasminogen activator treatment in acute ischemic stroke patients 17 .…”

Section: Introductionmentioning

confidence: 89%

Ischemia‐reperfusion injury of brain induces endothelial‐mesenchymal transition and vascular fibrosis via activating let‐7i/TGF‐βR1 double‐negative feedback loop

Chen

Wang

et al. 2020

FASEB j.

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Let-7i modulates the physical function and inflammation in endothelial cells (ECs).However, whether the let-7i of ECs involves in brain vasculature and ischemic stroke is unknown. Using inducible Cadherin5-Cre lineage-tracking mice, a loxp-RNAsponge conditional knockdown of let-7 in ECs-induced increase of transforming growth factor-β receptor type 1 (TGF-βR1), endothelial-mesenchymal transition (endMT), vascular fibrosis, and opening of the brain-blood barrier (BBB). By this lineage-tracking mice, we found that ECs underwent endMT after transient middle cerebral artery occlusion (MCAO). Through specifically overexpressed let-7i in ECs, we found that it reduced TGF-βR1, endMT, and vascular fibrosis. Furthermore, this overexpression reduced the infarct volume and leakage of the BBB, and improved the neurological function. Further, the expression of let-7i decreased after MCAO, but was reversed by antagonist of TGF-βR1 or inhibition of Mek phosphorylation.And the inhibition of Mek attenuated the vascular fibrosis after MCAO. In summary, we concluded that ischemic stroke activates a let-7i/TGF-βR1 double-negative feedback loop, thereby inducing endMT and vascular fibrosis. These results suggest that endMT is a potential target for the treatment of cerebral vascular fibrosis.

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“…At present, the diagnosis of stroke was mainly depended on the traditional neurological imaging methods, for example, magnetic resonance imaging (MRI) and computed tomography (CT) capabilities; however, not all hospitals were equipped with the equipment, and many patients, especially in the developing countries, cannot afford the high costs. On the other hand, the examination of the circulating biomarkers has now been considered as fast and inexpensive methods for the diagnosis of disease or evaluation of the clinical outcomes . Therefore, to identify novel circulating diagnostic and prognostic marker for ACI is in a great demand.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, the examination of the circulating biomarkers has now been considered as fast and inexpensive methods for the diagnosis of disease or evaluation of the clinical outcomes. 8,9 Therefore, to identify novel circulating diagnostic and prognostic marker for ACI is in a great demand.…”

Section: Introductionmentioning

confidence: 99%

Plasma level of miR‐99b may serve as potential diagnostic and short‐term prognostic markers in patients with acute cerebral infarction

Zhang

et al. 2020

Clinical Laboratory Analysis

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Objective The aim of the present study is to explore the potential diagnostic and prognostic value of plasma levels of miR‐99 family for patients with acute cerebral infarction (ACI). Methods A total of 112 patients who have been diagnosed with ACI were enrolled in this study, and 112 healthy volunteers were served as the controls. The plasma of the patients and controls were collected, and total RNAs were isolated, and the expression levels of miR‐99a, miR‐99b, and miR‐100 in the plasma of patients and controls were compared determined by RT‐qPCR methods; moreover, the receiver operating characteristic (ROC) curve has been drawn to determine whether the plasma levels of miR‐99b can distinguish patients with ACI from the controls; furthermore, the short‐term prognosis of the patients was evaluated by glasgow outcome scale (GOS), and the correlation between the plasma levels of miR‐99b and the GOS of the patients was evaluated. Finally, the correlation between the plasma level of miR‐99 and VEGF of ACI patients was analyzed. Results It was observed that miR‐99b was significantly decreased in the plasma of ACI patients compared with the healthy controls (P < .01), while the plasma levels of miR‐99a and miR‐100 showed no significant differences between the patients with ACI and the healthy controls; moreover, the area under the curve (AUC) of miR‐99b for the diagnosis of ACI was 0.8882 (95% confidence interval (CI), 0.8451‐0.9313), suggesting that plasma level of miR‐99b is a sensitive marker to distinguish patients with ACI from the healthy volunteers; furthermore, the serum level of miR‐99b was negatively correlated with GOS score of the patients (r = −.56, P < .001); finally, the plasma level of miR‐99b was negatively correlated with the levels of VEGF (r = −.3013, P = .0012). Conclusion miR‐99b was down‐regulated in plasma of patients with ACI, and plasma level of miR‐99b may be a potential diagnostic and prognostic marker for the diagnosis and treatment of ACI.

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Plasma let-7i and miR-15a expression are associated with the effect of recombinant tissue plasminogen activator treatment in acute ischemic stroke patients

Cited by 18 publications

References 22 publications

Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study

Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study

Ischemia‐reperfusion injury of brain induces endothelial‐mesenchymal transition and vascular fibrosis via activating let‐7i/TGF‐βR1 double‐negative feedback loop

Plasma level of miR‐99b may serve as potential diagnostic and short‐term prognostic markers in patients with acute cerebral infarction

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