Faculty of Medicine, Department of Cardiology, Marmara University, Yildiz Caddesi Konak Apartmani No: 43/24, Besiktas/Istanbul, 34353, Turkey.
Mol Cell Biochem. 2009 Nov;331(1-2):9-17. doi: 10.1007/s11010-009-0139-9. Epub 2009 May 7.
There is a great need for the identification of biomarkers for the early diagnosis of atherosclerosis and the agents to prevent its progression. The aim of this study was to explore the effect of 24 week of nebivolol (a third-generation vasodilatory beta-blocker) treatment on serum protein profiles in Apo E(-/-) mice during atherosclerosis progression. Nebivolol treated and non-treated (the control group) groups consisted of 10 genetically modified homozygous Apo E(-/-) mice. Proteomic analyses were performed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) in the serum samples from the nebivolol treated and non-treated Apo E(-/-) mice. The protein profiles obtained using three different chips, CM10 (weak cation-exchange), H50 (reverse phase), and IMAC30-Cu(2+) (immobilized metal affinity capture) were statistically analyzed using the ProteinChip data manager 3.0 program. At the end of 24 week of nebivolol-treatment period, a total of 662 protein/peptide clustering peaks were detected using 12 different conditions and reading with high and low intensity laser energy. The highest total number of protein/peptide clusters was found on H50 chip array. The peak intensities of 95 of the 662 protein/peptide clusters were significantly different in the nebivolol-treated atherosclerotic group in comparison to the non-treated control mice groups (P < 0.05). Forty-three protein/peptides were up-regulated (high signal intensity) while 52 protein/peptides had lower signal intensity (down-regulated) in the nebivolol-treated atherosclerotic group. The proteomic profiles of nebivolol-treated Apo E(-/-) mice were different than the control group indicating a potential role of nebivolol in atherosclerosis. Our study contributes to understand the efficacy of nebivolol on serum protein/peptide profiles during atherosclerosis development.
对于动脉粥样硬化的早期诊断和预防其进展的生物标志物的鉴定存在巨大需求。本研究旨在探索在动脉粥样硬化进展过程中,24 周的比索洛尔(第三代血管扩张β受体阻滞剂)治疗对 ApoE(-/-)小鼠血清蛋白谱的影响。比索洛尔治疗组和未治疗组(对照组)各包含 10 只基因修饰的纯合子 ApoE(-/-)小鼠。使用表面增强激光解吸/电离飞行时间质谱(SELDI-TOF MS)在比索洛尔治疗和未治疗的 ApoE(-/-)小鼠的血清样本中进行蛋白质组学分析。使用三种不同的芯片(CM10(弱阳离子交换)、H50(反相)和 IMAC30-Cu(2+)(固定化金属亲和捕获))获得的蛋白质图谱使用 ProteinChip 数据管理器 3.0 程序进行统计学分析。在比索洛尔治疗 24 周结束时,使用 12 种不同条件和高低激光能量读取共检测到 662 个蛋白质/肽聚类峰。在 H50 芯片阵列上发现了最多的蛋白质/肽聚类。与未治疗的对照组相比,在比索洛尔治疗的动脉粥样硬化组中,662 个蛋白质/肽聚类中的 95 个峰强度明显不同(P <0.05)。43 种蛋白质/肽呈上调(高信号强度),52 种蛋白质/肽的信号强度较低(下调)在比索洛尔治疗的动脉粥样硬化组中。比索洛尔治疗的 ApoE(-/-)小鼠的蛋白质组图谱与对照组不同,表明比索洛尔在动脉粥样硬化中可能发挥作用。我们的研究有助于了解比索洛尔在动脉粥样硬化发展过程中对血清蛋白质/肽谱的疗效。