Integrated Left Ventricular Global Transcriptome and Proteome Profiling in Human End-Stage Dilated Cardiomyopathy.
Integrated Left Ventricular Global Transcriptome and Proteome Profiling in Human End-Stage Dilated Cardiomyopathy.
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DOI：
10.1371/journal.pone.0162669
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Dzimiri N
中科院分区：
文献类型：
--
作者：
Colak D;Alaiya AA;Kaya N;Muiya NP;AlHarazi O;Shinwari Z;Andres E;Dzimiri N
导致特发性扩张型心肌病（DCM）的疾病途径仍然难以捉摸。本研究调查了人类DCM的整体转录和翻译变化，以发现疾病生物标志物。我们使用相同的心肌组织从五个DCM心脏相比，五个非衰竭（NF）供体心脏的转录组分析使用ABI高密度寡核苷酸微阵列和蛋白质组表达与一维纳米Acquity液相色谱串联质谱的Synapt G2系统。我们确定了1262差异表达基因（DEG）和269蛋白质（DEP）之间的DCM病例和健康对照。最显著上调（>5倍）的蛋白质是GRK 5、AP 0A 2、IGHG 3、ANXA 6、HSP 90 AA 1和ATP 5C 1（p< 0.01）。另一方面，最显著下调的蛋白质是GSTM 5、COX 17、CAV 1和ANXA 3。在两个分析平台上至少有十种实体同时上调：GOT 1、ALDH 4A 1、PDHB、BDH 1、SLC 2A 11、HSP 90 AA 1、HSP 90 AB 1、H2 AFV、HSP A5和NDUFV 1。DEG和DEP的基因本体分析揭示了与代谢过程、生物合成过程、细胞组分组织、氧化磷酸化、糖酵解和ATP合成的改变、阿尔茨海默病、趋化因子介导的炎症和细胞因子信号传导途径相关的基因/蛋白质的富集的显著重叠。同时使用转录组和蛋白质组表达来评估DCM的全球变化，已经鉴定出16种常见的改变实体以及新的基因、蛋白质和途径，其心脏功能尚未被破译。这些数据应有助于更好地管理这一疾病。
The disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are still elusive. The present study investigated integrated global transcriptional and translational changes in human DCM for disease biomarker discovery. We used identical myocardial tissues from five DCM hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the ABI high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system. We identified 1262 differentially expressed genes (DEGs) and 269 proteins (DEPs) between DCM cases and healthy controls. Among the most significantly upregulated (>5-fold) proteins were GRK5, APOA2, IGHG3, ANXA6, HSP90AA1, and ATP5C1 (p< 0.01). On the other hand, the most significantly downregulated proteins were GSTM5, COX17, CAV1 and ANXA3. At least ten entities were concomitantly upregulated on the two analysis platforms: GOT1, ALDH4A1, PDHB, BDH1, SLC2A11, HSP90AA1, HSP90AB1, H2AFV, HSPA5 and NDUFV1. Gene ontology analyses of DEGs and DEPs revealed significant overlap with enrichment of genes/proteins related to metabolic process, biosynthetic process, cellular component organization, oxidative phosphorylation, alterations in glycolysis and ATP synthesis, Alzheimer’s disease, chemokine-mediated inflammation and cytokine signalling pathways. The concomitant use of transcriptome and proteome expression to evaluate global changes in DCM has led to the identification of sixteen commonly altered entities as well as novel genes, proteins and pathways whose cardiac functions have yet to be deciphered. This data should contribute towards better management of the disease.
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影响因子：
6.1
作者：
Liu, Tingting;Chen, Le;Kim, Eunjung;Tran, Diana;Phinney, Brett S.;Knowlton, Anne A.
通讯作者：
Knowlton, Anne A.
RNA-Seq 鉴定了心力衰竭的新心肌基因表达特征。
影响因子：
4.4
作者：
Liu Y;Morley M;Brandimarto J;Hannenhalli S;Hu Y;Ashley EA;Tang WH;Moravec CS;Margulies KB;Cappola TP;Li M;MAGNet consortium
通讯作者：
MAGNet consortium
影响因子：
24
作者：
Barth, Andreas S.;Kuner, Ruprecht;Sueltmann, Holger
通讯作者：
Sueltmann, Holger
影响因子：
4.5
作者：
Ghazalpour A;Bennett B;Petyuk VA;Orozco L;Hagopian R;Mungrue IN;Farber CR;Sinsheimer J;Kang HM;Furlotte N;Park CC;Wen PZ;Brewer H;Weitz K;Camp DG 2nd;Pan C;Yordanova R;Neuhaus I;Tilford C;Siemers N;Gargalovic P;Eskin E;Kirchgessner T;Smith DJ;Smith RD;Lusis AJ
通讯作者：
Lusis AJ
影响因子：
3.8
作者：
Al-Moghrabi, Nisreen;Nofel, Asmaa;Aboussekhra, Abdelilah
通讯作者：
Aboussekhra, Abdelilah