Circulating endothelial microvesicles and their carried miR-125a-5p: potential biomarkers for ischaemic stroke.

Circulating endothelial microvesicles and their carried miR-125a-5p: potential biomarkers for ischaemic stroke.
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循环内皮微泡及其携带的 miR-125a-5p:缺血性中风的潜在生物标志物

DOI:
10.1136/svn-2021-001476
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发表时间:
2023-04
影响因子:
5.9
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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内皮微泡(EMV)与内皮细胞(EC)的状态密切相关。我们前期的研究表明EMV可以通过转移其携带的miR-125 a-5 p对EC发挥保护作用。然而,循环EMV及其携带的miR-125 a-5 p是否可用作缺血性卒中(IS)的生物标志物仍然未知。我们招募了72名IS患者,60名高卒中风险患者和56名年龄匹配的对照组。检测循环EMV及其携带的miR-125 a-5 p(EMV-miR-125 a-5 p)水平。我们使用microRNA(miR)芯片研究了3例IS患者和3例匹配的健康对照者血浆EMV中miR的表达变化。采用短暂性大脑中动脉闭塞(tMCAO)建立小鼠缺血再灌注模型。IS患者EMV水平明显升高,以急性期最高,与颈动脉斑块、颈动脉内膜中层厚度(IMT)、美国国立卫生研究院卒中量表(NIHSS)、梗死体积呈正相关。而IS组EMV-miR-125 a-5 p水平明显降低,急性期最低,且与颈动脉斑块、IMT、NIHSS评分、梗死体积呈负相关。EMV和EMV-miR-125 a-5 p水平与大动脉粥样硬化亚组密切相关。重要的是,EMV和EMV-miR-125 a-5 p水平可以作为独立的危险因素,IS的受试者工作特征曲线(AUC)分别达到0.720和0.832,并且在它们组合后升高至0.881。在IS小鼠模型中,与溶媒组相比,对照组和n-EMV组脑梗死体积和神经功能缺损评分均减小,脑血流量增加,而IS组和OGD-EMV组则加重了tMCAO所致的脑缺血损伤。此外,我们观察到OGD EMVmiR-125 a-5 p可以部分改善IS后OGD EMV诱导的脑损伤。这些研究结果表明,循环EMV和EMV-miR-125 a-5 p与IS的发生、发展、亚型和严重程度密切相关,它们可以作为IS的创新生物标志物和治疗靶点,尤其是当它们联合使用时。
Endothelial microvesicles (EMVs) are closely associated with the status of endothelial cells (ECs). Our earlier study has shown that EMVs could exert protective roles in ECs by transferring their carried miR-125a-5p. However, whether circulating EMVs and their carried miR-125a-5p can be used as biomarkers in ischaemic stroke (IS) are remain unknown. We recruited 72 subjects with IS, 60 subjects with high stroke risk and 56 age-matched controls. The circulating EMVs and their carried miR-125a-5p (EMV-miR-125a-5p) levels were detected. We used microRNA (miR) array to study expression changes of miRs in plasma EMVs samples of three IS patients and three matched healthy controls. Transient middle cerebral artery occlusion (tMCAO) was used to establish IS mouse model. EMVs level was obviously elevated in IS patients, with the highest level in acute stage, and was positively related to carotid plaque, carotid intima–media thickness (IMT), National Institutes of Health Stroke Scale (NIHSS), infarct volume. On the contrary, we observed that EMV-miR-125a-5p level was obviously reduced in IS, with the lowest level in acute stage, and was negatively correlated with carotid plaque, IMT, NIHSS scores, infarct volume. EMVs and EMV-miR-125a-5p levels were closely related with large artery atherosclerosis subgroup. Importantly, EMVs and EMV-miR-125a-5p levels could serve as independent risk factors, and receiver operating characteristic curve achieved an area under curve (AUC) of 0.720 and 0.832 for IS, respectively, and elevated to 0.881 after their combination. In IS mouse model, control EMVs or n-EMVs administration could decrease the infarct volume and neurological deficit score, while increase the cerebral blood flow of IS mice compared with vehicle group, while IS EMVs or oxygen and glucose deprivation (OGD)-EMVs administration aggravated the tMCAO induced ischaemic injury. In addition, we observed that OGD EMVmiR-125a-5p could partially ameliorate the OGD EMVs induced brain injury after IS. These findings demonstrate that circulating EMVs and EMV-miR-125a-5p are closely related with the occurrence, progress, subtypes and severity of IS, and they can serve as innovative biomarkers and therapeutic targets for IS, especially when they are combined.
DOI: 10.1007/s12265-013-9508-6
发表时间: 2013-10
影响因子: 3.4
作者:
Jin, Rong;Liu, Lin;Zhang, Shihao;Nanda, Anil;Li, Guohong
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发表时间: 2017-08
期刊: Circulation. Cardiovascular genetics
影响因子: --
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