MicroRNA and Hemostasis Profile of Carotid Atherosclerosis.

MicroRNA and Hemostasis Profile of Carotid Atherosclerosis.
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DOI:
10.3390/ijms231810974
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发表时间:
2022-09-19
影响因子:
5.6
通讯作者:
Tanashyan, Marine M.
Tanashyan, Marine M.
中科院分区:
生物学2区
文献类型:
--
作者:
Raskurazhev, Anton A.;Kuznetsova, Polina, I;Shabalina, Alla A.;Tanashyan, Marine M.

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颈动脉粥样硬化(CA)是缺血性脑卒中的重要危险因素。我们描述了中度和晚期颈动脉粥样硬化患者的 miRNA 和止血谱,并阐明了与止血激活的潜在相关性。一项前瞻性病例对照研究纳入了 61 名有颈动脉粥样硬化证据的患者(通过超声检查)。根据颈动脉狭窄程度将研究人群分为几组:60% 或以上(高级)和 <60%(中度)。所有患者均接受了以下血液检查:一般血液检查、止血参数和 microRNA。使用白细胞RNA纯化试剂盒(NORGEN Biotec Corp., Thorold, ON, Canada)提取微小RNA;通过 RT-PCR 进行 miRNA 定量。使用 RSudio 以 R 编程语言(v. 4.1.0)进行统计分析。 MicroRNA 表达谱根据 CA 程度而不同。颈动脉狭窄 ≥60% 的患者中 MiR-33a-5p/3p 水平较高(分别为 42.70 和 42.45 vs 38.50 和 38.50,p < 0.05)。 miR-126-5p 水平几乎完全分离:中度 CA 组为 9.50,而晚期 CA 组为 5.25 (p < 0.001)。中度 CA 组中的 MiR-29-5p 较高:28.60 [25.50;33.05] 高于晚期 CA 组:25.75 [24.38;29.50] (p = 0.086);中度 CA 组中的 miR-29-3p 也较高:10.36 [8.60;14.99] 高于晚期 CA 组:8.46 [7.47;10.3] (p = 0.001)。按组配对相关分析显示,中度 CA 组中至少存在三个具有显着正相关性的簇:miR-29-3p 与因子 V 和 XII(分别为 r = 0.53 和 r = 0.37,p < 0.05); miR-21-5p 与 ADAMTS13、红细胞沉降率和 D-二聚体(分别为 r = 0.42、r = 0.36 和 r = 0.44,p < 0.05);狭窄程度与 miR-33a-5p/3p 和因子 VIII 水平的关系(分别为 r = 0.43(两者)和 r = 0.62,p < 0.05)。 CA 患者的止血参数并未显示显着变化:唯一具有统计学意义的差异涉及因子 VIII、纤溶酶原以及(边缘显着的)ADAMTS-13 和蛋白 C。miR-126-5p 表达的下调已被确定为晚期颈动脉粥样硬化的一种有前途的生物标志物,具有高特异性和敏感性。相关聚类分析显示颈动脉粥样硬化背景下 miRNA 与止血激活之间的潜在相互作用。
Carotid atherosclerosis (CA) is an important risk factor for ischemic stroke. We described the miRNA and hemostasis profile of patients with moderate and advanced stages of carotid atherosclerosis and elucidated potential correlations with hemostatic activation. A prospective case-control study included 61 patients with evidence of carotid atherosclerosis (via ultrasound). The study population was divided into groups depending on the degree of carotid artery stenosis: 60% or more (advanced) and <60% (moderate). All patients underwent the following blood tests: general blood test, hemostatic parameters and microRNA. Extraction of microRNA was performed using Leukocyte RNA Purification Kit (NORGEN Biotec Corp., Thorold, ON, Canada); miRNA quantification was performed via RT-PCR. Statistical analysis was performed in R programming language (v. 4.1.0) using RSudio. MicroRNA expression profile was different depending on CA degree. MiR-33a-5p/3p levels were higher in patients with ≥60% carotid stenosis (42.70 and 42.45 versus 38.50 and 38.50, respectively, p < 0.05). Almost complete separation can be visualized with the levels of miR-126-5p: 9.50 in the moderate CA group versus 5.25 in the advanced CA (p < 0.001). MiR-29-5p was higher in the moderate CA group: 28.60 [25.50;33.05] than in advanced CA group: 25.75 [24.38;29.50] (p = 0.086); miR-29-3p was also higher in the moderate CA group: 10.36 [8.60;14.99] than in advanced CA group: 8.46 [7.47;10.3] (p = 0.001). By-group pairwise correlation analyses revealed at least three clusters with significant positive correlations in the moderate CA group: miR-29-3p with factors V and XII (r = 0.53 and r = 0.37, respectively, p < 0.05); miR-21-5p with ADAMTS13, erythrocyte sedimentation rate and D-dimer (r = 0.42, r = 0.36 and r = 0.44, respectively, p < 0.05); stenosis degree with miR-33a-5p/3p and factor VIII levels (r = 0.43 (both) and r = 0.62, respectively, p < 0.05). Hemostasis parameters did not reveal significant changes in CA patients: the only statistically significant differences concerned factor VIII, plasminogen and (marginally significant) ADAMTS-13 and protein C. Down-regulation of miR-126-5p expression has been identified as a promising biomarker of advanced carotid atherosclerosis with high specificity and sensitivity. Correlation cluster analysis showed potential interplay between miRNAs and hemostatic activation in the setting of carotid atherosclerosis.
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