Abstract:
With a global towering prevalence of index acute myocardial infarction (nonrecurrent MI, NR-MI), a high incidence of recurrent MI (R-MI) has emerged in recent decades. Despite the extensive occurrence, the promising predictors of R-MI have been elusive within the cohort of survivors. This study investigates and validates the involvement of distinct gene expressions in R-MI and NR-MI. Bioinformatics tools were used to identify DEGs from the GEO dataset, functional annotation, pathway enrichment analysis, and the PPI network analysis to find hub genes. The validation of proposed genes was conceded by qRT-PCR and Western Blot analysis in experimentally induced NR-MI and R-MI models on a temporal basis. The temporal findings based on RT-PCR consequences reveal a significant and constant upregulation of the UBE2N in the NR-MI model out of the proposed three DEGs (UBE2N, UBB, and TMEM189), while no expression was reported in the R-MI model. Additionally, the proteomics study proposed five DEGs (IL2RB, NKG7, GZMH, CXCR6, and GZMK) for the R-MI model since IL2RB was spotted for significant and persistent downregulation with different time points. Further, Western Blot analysis validated these target genes\' expressions temporally. I/R-induced NR-MI and R-MI models were confirmed by the biochemical parameters (CKMB, LDH, cTnI, serum nitrite/nitrate concentration, and inflammatory cytokines) and histological assessments of myocardial tissue. These results underscore the importance of understanding genetic mechanisms underlying MI and highlight the potential of UBE2N and IL2RB as biomarkers for non-recurrent and recurrent MI, respectively.
摘要:
在全球范围内,急性心肌梗死指数(非复发性MI,NR-MI),近几十年来,复发性MI(R-MI)的发病率较高.尽管发生了广泛的事件,在幸存者队列中,R-MI的有希望的预测因子一直难以捉摸.这项研究调查并验证了R-MI和NR-MI中不同基因表达的参与。生物信息学工具用于从GEO数据集中识别DEG,功能注释,途径富集分析,和PPI网络分析,寻找枢纽基因。通过qRT-PCR和Western印迹分析在实验诱导的NR-MI和R-MI模型中在时间基础上证实了所提出的基因的验证。基于RT-PCR结果的时间发现揭示了在所提出的三个DEG(UBE2N,UBB,和TMEM189),而R-MI模型中无表达报道。此外,蛋白质组学研究提出了五个DEGs(IL2RB,NKG7,GZMH,CXCR6和GZMK)用于R-MI模型,因为IL2RB在不同时间点被发现具有显著和持续的下调。Further,Western印迹分析在时间上验证了这些靶基因的表达。I/R诱导的NR-MI和R-MI模型通过生化参数(CKMB,LDH,cTnI,血清亚硝酸盐/硝酸盐浓度,和炎性细胞因子)和心肌组织的组织学评估。这些结果强调了理解MI的遗传机制的重要性,并强调了UBE2N和IL2RB作为非复发性和复发性MI的生物标志物的潜力。分别。