Analysis of MicroRNAs Associated With Carotid Atherosclerotic Plaque Rupture With Thrombosis.
Analysis of MicroRNAs Associated With Carotid Atherosclerotic Plaque Rupture With Thrombosis.
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DOI：
10.3389/fgene.2021.599350
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发表时间：
2021
影响因子：
3.7
通讯作者：
Pu J
中科院分区：
文献类型：
--
作者：
Nie P;Yang F;Wan F;Jin S;Pu J
动脉粥样硬化是一种进行性血管壁炎性疾病，动脉粥样硬化易损斑块的破裂是全球发病率和死亡率的主要原因。本研究旨在探讨ApoE基因敲除小鼠斑块破裂和血栓形成的潜在机制。建立自发性斑块破裂模型，分别于术后1、2、4、6、8、12、16周采集左颈动脉组织。根据斑块破裂程度，将斑块分为（1）对照组、（2）动脉粥样硬化斑块组和（3）斑块破裂组。巨噬细胞（CD 68），MMP-8和MMP-13的活性通过免疫荧光法测定。ELISA法检测细胞因子和炎症标志物。取左颈动脉标本，采用微RNA芯片技术检测其miRNA表达水平。生物信息学分析在三个水平进行：（2）与（1），（3）与（2），并再次在七个时间序列分析。斑块破裂伴血栓和斑块内出血结果在8周时达到峰值，此后下降。在斑块巨噬细胞和脂质的数量、基质金属蛋白酶的表达以及动脉粥样硬化和血浆细胞因子水平中观察到类似的趋势。miRNA芯片显示，与对照组相比，动脉粥样硬化斑块组中miR-322- 5 p和miR-206- 3 p特异性上调。同时，与动脉粥样硬化斑块组相比，斑块破裂组中miR-466 h-5 p特异性上调。斑块破裂和血栓形成的最高发生率发生在术后8周。miR-322- 5 p和miR-206- 3 p可能与动脉粥样硬化斑块的形成有关。miR-466 h-5 p可能通过动脉粥样硬化相关通路促进动脉粥样硬化斑块破裂。
Atherosclerosis is a progressive vascular wall inflammatory disease, and the rupture of atherosclerotic vulnerable plaques is the leading cause of morbidity and mortality worldwide. This study intended to explore the potential mechanisms behind plaque rupture and thrombosis in ApoE knockout mice. The spontaneous plaque rupture models were established, and left carotid artery tissues at different time points (1-, 2-, 4-, 6-, 8-, 12-, and 16-week post-surgery) were collected. By the extent of plaque rupture, plaque was defined as (1) control groups, (2) atherosclerotic plaque group, and (3) plaque rupture group. Macrophage (CD68), MMP-8, and MMP-13 activities were measured by immunofluorescence. Cytokines and inflammatory markers were measured by ELISA. The left carotid artery sample tissue was collected to evaluate the miRNAs expression level by miRNA-microarray. Bioinformatic analyses were conducted at three levels: (2) vs. (1), (3) vs. (2), and again in seven time series analysis. The plaque rupture with thrombus and intraplaque hemorrhage results peaked at 8 weeks and decreased thereafter. Similar trends were seen in the number of plaque macrophages and lipids, the expression of matrix metalloproteinase, and the atherosclerotic and plasma cytokine levels. MiRNA-microarray showed that miR-322-5p and miR-206-3p were specifically upregulated in the atherosclerotic plaque group compared with those in the control group. Meanwhile, miR-466h-5p was specifically upregulated in the plaque rupture group compared with the atherosclerotic plaque group. The highest incidence of plaque rupture and thrombosis occurred at 8 weeks post-surgery. miR-322-5p and miR-206-3p may be associated with the formation of atherosclerotic plaques. miR-466h-5p may promote atherosclerotic plaque rupture via apoptosis-related pathways.
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