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Right Ventricular Protein Expression Profile in End-Stage Heart Failure:

机译:终末期心力衰竭的右心室蛋白表达谱:

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Little is known about the right ventricular (RV) proteome in human heart failure (HF), including possible differences compared to the left ventricular (LV) proteome. We used 2-dimensional differential in-gel electrophoresis (pH: 4–7, 10–150 kDa), followed by liquid chromatography tandem mass spectrometry, to compare the RV and LV proteomes in 12 explanted human hearts. We used Western blotting and multiple-reaction monitoring for protein verification and RNA sequencing for messenger RNA and protein expression correlation. In all 12 hearts, the right ventricles (RVs) demonstrated differential expression of 11 proteins relative to the left ventricles (LVs), including lesser expression of CRYM, TPM1, CLU, TXNL1, and COQ9 and greater expression of TNNI3, SAAI, ERP29, ACTN2, HSPB2, and NDUFS3. Principal-components analysis did not suggest RV-versus-LV proteome partitioning. In the nonischemic RVs (n = 6), 7 proteins were differentially expressed relative to the ischemic RVs (n = 6), including increased expression of CRYM, B7Z964, desmin, ANXA5, and MIME and decreased expression of SERPINA1 and ANT3. Principal-components analysis demonstrated partitioning of the nonischemic and ischemic RV proteomes, and gene ontology analysis identified differences in hemostasis and atherosclerosis-associated networks. There were no proteomic differences between RVs with echocardiographic dysfunction (n = 8) and those with normal function (n = 4). Messenger RNA and protein expression did not correlate consistently, suggesting a major role for RV posttranscriptional protein expression regulation. Differences in contractile, cytoskeletal, metabolic, signaling, and survival pathways exist between the RV and the LV in HF and may be related to the underlying HF etiology and differential posttranscriptional regulation.
机译:对人心力衰竭(HF)中的右心室(RV)蛋白质组知之甚少,包括与左心室(LV)蛋白质组相比可能的差异。我们使用了二维差分凝胶电泳(pH:4-7、10-150 kDa),然后进行液相色谱串联质谱分析,比较了12个植入人体心脏中的RV和LV蛋白质组。我们使用蛋白质印迹和多反应监测进行蛋白质验证,并使用RNA测序检测信使RNA和蛋白质表达相关性。在所有12个心脏中,右心室(RVs)相对于左心室(LVs)表现出11种蛋白质的差异表达,包括CRYM,TPM1,CLU,TXNL1和COQ9的表达较少,而TNNI3,SAAI,ERP29, ACTN2,HSPB2和NDUFS3。主成分分析未提示RV对LV蛋白质组分配。在非缺血性RVs(n = 6)中,相对于缺血性RVs(n = 6),差异表达7种蛋白质,包括CRYM,B7Z964,desmin,ANXA5和MIME的表达增加,而SERPINA1和ANT3的表达减少。主成分分析显示了非缺血性和缺血性RV蛋白质组的划分,基因本体分析确定了止血和动脉粥样硬化相关网络的差异。超声心动图功能不全的RVs(n = 8)和功能正常的RVs(n = 4)之间没有蛋白质组学差异。信使RNA和蛋白质的表达并不始终相关,这表明RV转录后蛋白质表达调控的主要作用。 HF的RV和LV之间存在收缩,细胞骨架,代谢,信号传导和存活途径方面的差异,可能与潜在的HF病因和转录后调控不同有关。

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