Proteomic profiling during atherosclerosis progression using SELDI-TOF-MS: Effect of darbepoetin treatment
Proteomic profiling during atherosclerosis progression using SELDI-TOF-MS: Effect of darbepoetin treatment
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DOI：
10.1016/j.acthis.2009.04.003
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发表时间：
2010-01-01
影响因子：
2.5
通讯作者：
Ozben, Tomris
中科院分区：
文献类型：
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作者：
Dursun, Evrim;Monari, Emanuela;Ozben, Tomris
动脉粥样硬化导致的动脉狭窄可能导致充血性心力衰竭（CHF）。在载脂蛋白E缺陷（Apo E-/-）小鼠模型中进行动脉粥样硬化研究是有利的，与人类相比，载脂蛋白E缺陷（Apo E-/-）小鼠模型发展动脉粥样硬化非常迅速。达贝泊汀是一种合成的促红细胞生成素类似物，可刺激红细胞生成。本研究的目的是探讨16周达贝泊苷治疗对动脉粥样硬化进展期间Apo E-/-小鼠血清蛋白谱的影响。使用表面增强激光解吸/电离飞行时间质谱法（SELDI-TOF-MS）对达贝泊汀给药组和未给药（对照）Apo E-/-小鼠组进行血清蛋白质组学分析。使用三种不同的芯片，CM-10（弱阳离子交换），H50（反相）和IMAC-30（固定化金属亲和捕获），获得的蛋白质谱进行统计分析，使用ProteinChip数据管理器3.0程序。在达贝泊苷治疗16周结束时，达贝泊苷组和对照组小鼠之间动脉粥样硬化病变的大小和程度没有显著差异。相比之下，145个蛋白质/肽簇峰（>5 kDa）在达贝泊汀和对照小鼠组之间的峰强度具有统计学显著差异（p < 0.05）。发现达贝泊汀处理的Apo E-/-小鼠的蛋白质组特征与对照组不同，表明达贝泊汀在动脉粥样硬化中具有潜在的有益作用。我们的研究有助于了解动脉粥样硬化发展过程中达贝泊苷对蛋白/肽表达的影响。(C)2009年Elsevier GmbH。All rights reserved.
Narrowing of the arteries due to atherosclerosis may lead to congestive heart failure (CHF). It is advantageous to perform atherosclerosis studies in apolipoprotein E-deficient (Apo E-/-) mice models, which develop atherosclerosis very rapidly in comparison to humans. Darbepoetin is a synthetic erythropoietin analogue and stimulates erythropoiesis. The aim of this study was to explore the effect of 16 weeks of darbepoetin treatment on serum protein profiles in Apo E-/- mice during atherosclerosis progression. Serum proteomic analyses were performed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) in the darbepoetin-treated and non-treated (control) Apo E-/- mice groups. The protein profiles obtained using three different chips, CM-10 (weak cation exchange), H50 (reversed-phase) and IMAC-30 (immobilized metal affinity capture), were statistically analyzed using the ProteinChip data manager 3.0 program. At the end of 16 weeks of darbepoetin treatment, there was no significant difference in the size and degree of atherosclerotic lesions between the darbepoetin and control mice groups. In contrast, 145 protein/peptide-clustering peaks, >5 kDa, had statistically significant differences in their peak intensities between the darbepoetin and control mice groups (p < 0.05). That the proteonnic profiles of darbepoetin-treated Apo E-/- mice were found to differ from those of the control group indicates a potential beneficial role of darbepoetin in atherosclerosis. Our study contributes to understanding the effects of darbepoetin on protein/peptide expressions during atherosclerosis development. (C) 2009 Elsevier GmbH. All rights reserved.