Su Qiang, Li Lang, Zhao Jinmin, Sun Yuhan, Yang Huafeng
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
Cell Physiol Biochem. 2017;43(3):1012-1024. doi: 10.1159/000481699. Epub 2017 Oct 2.
BACKGROUND/AIMS: Coronary microembolization (CME) is a serious complication of coronary heart disease and is considered as a strong predictor of poor long-term prognosis and major cardiac adverse events. Here, we identified differentially expressed microRNAs (miRNAs) in the myocardial tissue of CME pigs, and predicted and analyzed the possible functions of their target genes.
Twelve Bama mini-pigs were randomly assigned to the sham and CME group (n = 6 in each group). The two groups were compared with regard to heart function, area of infarction, cardiomyocyte apoptosis, and myocardial expression of TNF-α, IL-1β and IL-6. Further, miRNA chip analysis was used to screen for differentially expressed miRNAs, and the results were validated by real-time PCR. Bioinformatics methods were used to predict and analyze the functions of the target genes of the identified miRNAs.
The model CME pigs showed significantly increased expression of TNF-α, IL-1β and IL-6, as well as micro-infarction lesions and cell apoptosis in the myocardial tissue. Thus, the model was established successfully. In the myocardial tissue of the CME pigs, the expression of ssc-miR-92b-5p, ssc-miR-491, ssc-miR-874, ssc-miR-425-3p, ssc-miR-376a-5p, ssc-miR-370, ssc-miR-30c-3p, ssc-miR-493-5p and ssc-miR-323 was significantly increased, whereas the expression of ssc-miR-136 and ssc-miR-142-3p was significantly decreased. GO and KEGG pathway analysis indicated that the target genes of these miRNAs are mainly associated with cell proliferation, apoptosis, necrosis, inflammation, and fibrosis.
The differentially expressed miRNAs identified in the myocardial tissue of CME pigs could be new biomarkers or potential treatment targets for CME.
背景/目的:冠状动脉微栓塞(CME)是冠心病的一种严重并发症,被认为是长期预后不良和主要心脏不良事件的有力预测指标。在此,我们鉴定了CME猪心肌组织中差异表达的微小RNA(miRNA),并对其靶基因的可能功能进行了预测和分析。
将12只巴马小型猪随机分为假手术组和CME组(每组n = 6)。比较两组的心功能、梗死面积、心肌细胞凋亡以及心肌组织中TNF-α、IL-1β和IL-6的表达。此外,采用miRNA芯片分析筛选差异表达的miRNA,并通过实时PCR验证结果。利用生物信息学方法预测和分析所鉴定miRNA靶基因的功能。
模型CME猪心肌组织中TNF-α、IL-1β和IL-6的表达显著增加,同时出现微梗死病变和细胞凋亡。因此,成功建立了模型。在CME猪的心肌组织中,ssc-miR-92b-5p、ssc-miR-491、ssc-miR-874、ssc-miR-425-3p、ssc-miR-376a-5p、ssc-miR-370、ssc-miR-30c-3p、ssc-miR-493-5p和ssc-miR-323的表达显著增加,而ssc-miR-136和ssc-miR-142-3p的表达显著降低。基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析表明,这些miRNA的靶基因主要与细胞增殖、凋亡、坏死、炎症和纤维化相关。
在CME猪心肌组织中鉴定出的差异表达miRNA可能是CME的新生物标志物或潜在治疗靶点。