The three genes of vertebrate transcriptional extension factor TFIIS include Tcea1, 2,3. The paper pointed out that P-TEFB appears to be dynamically divided between the active state and the inactive state, indicating that its transcriptional control can be regulated ( 3). It was found that some transcription enlongation factors such as positive transcriptional extension factor (P-TEF) B plays a key role in myocardial hypertrophy response to pressure overload ( 2). In addition to the translation and transcriptional initiation steps, transcriptional prolongation involving RNA polymerase (Pol) II is now considered to be a key step in controlling full-length mRNA production ( 1). Transcription factors are an important type of gene transcription regulatory element. Therefore, identification of new therapeutic targets is urgently required. Despite numerous studies on the mechanisms of heart failure, clinical outcomes remain suboptimal and the mortality rate is still high. Initially, cardiac hypertrophy develops as an adaptive response to persistent pathological stimuli, but it often progresses to fibrosis, dysfunction, and ultimately heart failure. Heart failure is a rapidly growing public health concern and a leading cause of mortality. In PE induced cardiomyocyte hypertrophy, Tcea3 silencing results in decreased fatty acid utilization, decreased ATP synthesis and increased mitochondrial oxidative stress.Ĭonclusion: Our study identifies Tcea3 as a novel anti-cardiac remodeling target by regulating FAO and governing mitochondrial oxidative stress. Subsequently, RT-PCR results showed that knockdown of Tcea3 up-regulated Ces1d and Pla2g5 mRNA expression levels. GSEA and online tool ARCHS4 predict Tcea3 involved in fatty acid oxidation (FAO). Knockdown of Tcea3 aggravated cardiomyocyte hypertrophy induced by PE in NRVMs. The expression level of Tcea3 was downregulated during cardiac remodeling both in vivo and in vitro. Results: A total of 95 DEGs were identified and Tcea3 was negatively correlated with Nppa, Nppb and Myh7. Finally, MitoSOX staining was used to detect the effect of Tcea3 on mitochondrial oxidative stress, and the contents of NADP(H) and GSH/GSSG were detected by relevant kits. Furthermore, the changes of long-chain fatty acid respiration in NRVMs were detected using the Seahorse XFe24 Analyzer. Next, gene set enrichment analysis (GSEA) and the online tool ARCHS4 were used to predict the possible signaling pathways, and the fatty acid oxidation relevant pathways were enriched and then verified in NRVMs. By using RNA interference technology, the effect of transcription elongation factor A3 (Tcea3) silencing on PE-induced hypertrophy of neonatal rat ventricular myocytes (NRVMs) was detected. A mouse model of cardiac remodeling induced by transverse aortic constriction (TAC) was established to verify the expression of the interest gene during cardiac remodeling by RT-PCR and western blot. Correlation analysis and BioGPS online tool were used to detect the genes of interest. We identified differentially expressed genes (DEGs) by overlapping three Gene Expression Omnibus (GEO) datasets (GSE5500, GSE1621, and GSE36074). Methods: Comprehensive bioinformatics tools were used to screen genes related to pressure overload-induced cardiac hypertrophy. The aim of this study is to identify key genes associated with pathological cardiac hypertrophy by combining bioinformatics analyses with molecular biology experiments. Effective biomarkers and therapeutic targets for heart failure remain to be defined. 3Cardiovascular Research Institute, Wuhan University, Wuhan, Chinaīackground: Chronic pressure overload triggers pathological cardiac hypertrophy that eventually leads to heart failure.2Hubei Key Laboratory of Metabolic and Chronic Diseases, Renmin Hospital of Wuhan University, Wuhan, China.1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.Yingying Guo 1,2,†, Xian-feng Cen 1,2,†, Dan Li 1,2, Hong-liang Qiu 1,2, Ya-jie Chen 1,2, Meng Zhang 1,2, Si-hui Huang 1,2, Hao Xia 1,3* and Man Xu 1,2*
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