Myocyte enhancer factor 2A (MEF2A) plays an important role in cell proliferation, differentiation and survival. Functional deletion or mutation in MEF2A predisposes individuals to cardiovascular disease mainly caused by vascular endothelial dysfunction. However, the effect of the inhibition of MEF2A expression on human coronary artery endothelial cells (HCAECs) is unclear. In this study, expression of MEF2A was inhibited by specific small interference RNA (siRNA), and changes in mRNA profiles in response to MEF2A knockdown were analyzed using an Agilent human mRNA array. Silencing of MEF2A in HCAECs accelerated cell senescence and suppressed cell proliferation. Microarray analysis identified 962 differentially expressed genes (DEGs) between the MEF2A knockdown group and the negative control group. Annotation clustering analysis showed that the DEGs were preferentially enriched in gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to proliferation, development, survival, and inflammation. Furthermore, 61 of the 578 downregulated DEGs have at least one potential MEF2A binding site in the proximal promoter and were mostly enriched in the GO terms “reproduction” and “cardiovascular.” The protein–protein interaction network analyzed for the downregulated DEGs and the DEGs in the GO terms “cardiovascular” and “aging” revealed that PIK3CG, IL1B, IL8, and PRKCB were included in hot nodes, and the regulation of the longevity-associated gene PIK3CG by MEF2A has been verified at the protein level, suggesting that PIK3CG might play a key role in MEF2A knockdown induced HCAEC senescence. MEF2A knockdown accelerates HCAEC senescence, and the underlying molecular mechanism may be involved in down-regulation of the genes related with cell proliferation, development, inflammation and survival, in which PIK3CG may play a key role.

中文翻译：

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MEF2A改变了增殖，炎症相关基因的表达谱，其沉默诱导了人类冠状动脉内皮细胞的细胞衰老。

心肌细胞增强因子2A（MEF2A）在细胞增殖，分化和存活中起重要作用。MEF2A中的功能性缺失或突变使个体容易患上心血管疾病，这种疾病主要由血管内皮功能障碍引起。然而，MEF2A表达的抑制作用对人冠状动脉内皮细胞（HCAECs）尚不清楚。在这项研究中，MEF2A的表达被特定的小干扰RNA（siRNA）抑制，并使用安捷伦人mRNA阵列分析了响应MEF2A敲低的mRNA谱变化。在HCAEC中沉默MEF2A可以加速细胞衰老并抑制细胞增殖。微阵列分析鉴定了MEF2A敲除组和阴性对照组之间的962个差异表达基因（DEG）。注释聚类分析表明，DEGs优先富含基因本体论（GO）术语和与增殖，发育，存活和炎症有关的《京都议定书全书》。此外，在578个下调的DEG中，有61个在近端启动子中具有至少一个潜在的MEF2A结合位点，并且大多富含GO术语“生殖”和“心血管”。蛋白质-蛋白质相互作用网络分析了下调的DEGs和GO术语“心血管”和“衰老”中的DEGs，发现PIK3CG，IL1B，IL8和PRKCB包含在热结节中，并且长寿相关基因的调控MEF2A的PIK3CG已在蛋白质水平上得到验证，这表明PIK3CG可能在MEF2A抑制的HCAEC衰老中起关键作用。