Proteomic profiling of the human failing heart after left ventricular assist device support
Proteomic profiling of the human failing heart after left ventricular assist device support
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DOI：
10.1016/j.healun.2010.11.011
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发表时间：
2011-05-01
影响因子：
8.9
通讯作者：
Bovenschen, Niels
中科院分区：
文献类型：
--
作者：
de Weger, Roel A.;Schipper, Marguerite E. I.;Bovenschen, Niels
背景：左心室辅助装置（LVAD）支持通常用于心力衰竭患者作为心脏移植的桥梁。尽管在LVAD支持后心肌基因表达谱的改变已经很好地确立，但对蛋白质水平的影响在很大程度上仍不清楚。方法：采用荧光二维差异凝胶电泳分析扩张型心肌病（DCM）和缺血性心脏病（IHD）患者lvad前后心肌组织标本，并用质谱法鉴定差异表达蛋白。结果：在DCM组中，检测到16种蛋白从lvad前组织到lvad后组织的下调有统计学意义。在IHD患者中，发现了50个改变，包括上调（n = 12）和下调（n = 38）蛋白。在两组中鉴定的蛋白质部分重叠，包括来自细胞骨架和线粒体能量代谢的蛋白质。电镜显示，后一种变化与线粒体形态的严重异常相平行。DCM和IHD患者lvad后的蛋白质组在很大程度上模仿了非衰竭心脏的蛋白质谱。免疫吸附实验证实，DCM和IHD患者在LVAD支持后，丝氨酸蛋白酶抑制剂a-l-抗凝乳胰蛋白酶下调。结论：DCM和IHD患者lvad诱导的心脏重构与α -1-抗凝乳胰蛋白酶下调以及主要参与细胞骨架完整性和线粒体能量代谢的蛋白质表达谱的特异性萎缩变化有关。I心肺移植2011；2011国际心脏与肺移植学会。版权所有。
BACKGROUND: Left ventricular assist device (LVAD) support is commonly used in patients with heart failure as a bridge to heart transplantation. Whereas myocardial gene expression profile changes have been well established after LVAD support, the consequences on the protein level largely remain unclear.METHODS: F're-LVAD and post-LVAD myocardial tissue specimens from dilated cardiomyopathy (DCM) and ischemic heart disease (IHD) patients were analyzed by fluorescent 2-dimensional difference gel electrophoresis, and differentially expressed proteins were identified by mass spectrometry.RESULTS: In the DCM group, 16 proteins were detected that showed statistically significant down-regulation from pre-LVAD to post-LVAD tissue. In IHD patients, 50 alterations were found, including upregulated (n = 12) and downregulated (n = 38) proteins. The identified proteins in both groups partially overlapped and included proteins from cytoskeleton and mitochondrial energy metabolism. The latter changes were paralleled by severe abnormalities in mitochondrial morphology, as shown by electron microscopy. Post-LVAD proteomes of both DCM and IHD patients largely mimicked the protein profiles of non-failing hearts. Downregulation of the serine protease inhibitor a-l-antichymotrypsin in both DCM and IHD patients after LVAD support was confirmed by immunosorbent assay.CONCLUSIONS: LVAD-induced cardiac remodeling in DCM and IHD patients is associated with downregulation of alpha-1-antichymotrypsin and specific atrophic changes in protein expression profiles predominantly involved in cytoskeleton integrity and mitochondrial energy metabolism. I Heart Lung Transplant 2011;30:497-506 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.