Research Center of Neurology, 80, Volokolamskoe Shosse, 125367 Moscow, Russia.
Laboratory of Hemorheology, Hemostasis and Pharmacokinetics with Clinical Laboratory Diagnostics, Research Center of Neurology, 80 Volokolamskoye Shosse, 125367 Moscow, Russia.
Int J Mol Sci. 2024 Sep 18;25(18):10026. doi: 10.3390/ijms251810026.
Atherosclerosis is a chronic inflammatory disorder which remains the main cause of cardiovascular morbidity and mortality, with carotid atherosclerosis (CA) being a major cause of ischemic stroke. Epigenetic regulation plays a significant role in CA progression and stroke, yet the impact of circulating microRNA expression, associated with atherogenesis, has not been clearly defined. We included 81 patients with moderate-severe CA (mean age 67 ± 7 years, 53% male), 42% of whom had prior ipsilateral ischemic stroke (i.e., were symptomatic). A total of 24 miRs were identified and their plasma expression levels were measured. We observed that several microRNAs were up-regulated in stroke survivors, namely miR-200c-3p (30.6 vs. 29.7, = 0.047), miR-106b-3p (31.01 vs. 30.25, = 0.004), and miR-494-5p (39 vs. 33, < 0.001), while others (miR183-3p [25.5 vs. 28.6, < 0.001], miR-126-5p [35.6 vs. 37.1, = 0.03], and miR-216-3p [12.34 vs. 16.2, < 0.001]) had lower plasma levels in symptomatic patients. In a multivariable logistic regression model for symptomatic CA, the only miRs showing statistical significance were miR-106b-5p, miR-183-3p, miR-216-3p, and miR-494-5p. Cluster analysis demonstrated differential miR expression in CA patients depending on their stroke status. Epigenetic modulation, represented as complex interplay between circulating miRs of different atherogenic potential, may play a significant role in CA development and progression. In our study, we show possible candidates for future research regarding CA and stroke.
动脉粥样硬化是一种慢性炎症性疾病，仍然是心血管发病率和死亡率的主要原因，颈动脉粥样硬化（CA）是缺血性中风的主要原因。表观遗传调控在 CA 进展和中风中起着重要作用，但与动脉粥样硬化形成相关的循环 microRNA 表达的影响尚未明确界定。我们纳入了 81 名中重度 CA 患者（平均年龄 67 ± 7 岁，53%为男性），其中 42%有同侧缺血性中风（即有症状）。共鉴定出 24 个 miRs，并测量了它们的血浆表达水平。我们观察到，在中风幸存者中，几种 microRNAs 上调，即 miR-200c-3p（30.6 比 29.7， = 0.047）、miR-106b-3p（31.01 比 30.25， = 0.004）和 miR-494-5p（39 比 33， < 0.001），而其他 microRNAs（miR183-3p [25.5 比 28.6， < 0.001]、miR-126-5p [35.6 比 37.1， = 0.03]和 miR-216-3p [12.34 比 16.2， < 0.001]）在有症状的患者中血浆水平较低。在有症状的 CA 的多变量逻辑回归模型中，唯一具有统计学意义的 miRs 是 miR-106b-5p、miR-183-3p、miR-216-3p 和 miR-494-5p。聚类分析表明，根据患者的中风状态，CA 患者的 miR 表达存在差异。表观遗传调节，表现为不同动脉粥样硬化形成潜力的循环 miRs 之间的复杂相互作用，可能在 CA 的发展和进展中起着重要作用。在我们的研究中，我们展示了与 CA 和中风相关的未来研究的可能候选者。
