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[心血管蛋白质组学:未来心脏病学家面临的挑战与机遇]

[Cardiovascular proteomics: challenges and opportunities for cardiologists of the future].

作者信息

Banfi Cristina, Brioschi Maura, Tremoli Elena

机构信息

Centro Cardiologico Monzino IRCCS, Milano.

出版信息

G Ital Cardiol (Rome). 2013 Jul-Aug;14(7-8):495-503. doi: 10.1714/1308.14458.

Abstract

Proteomics is the study of the "proteome", that is the entire protein complement of a genome. However, it is well recognized that the proteome is far more complex than previously suggested by the "one-gene, one-protein" central dogma of biology. The proteome encompasses all proteins of a cell or organism at a given time, including not only those translated directly from genetic information but also the array of modified proteins arising from alternative splicing of transcripts and post-translational processing, resulting in modifications that have the potential to alter protein structure or biological function. As proteins are involved in virtually every cellular function, control every regulatory mechanism, and are modified in disease states, the proteome dictates the phenotype of the cell and, consequently, the tissue or organ that the cells comprise. This results in a dynamic, ongoing process of protein expression and modifications. The proteome thus consists of information from protein expression, post-translational modifications, processing and turnover, localization and time. Proteomics is aimed at identifying and characterizing these protein changes and, if applied to the field of cardiovascular sciences, it has the potential to reveal those proteins that are associated with pathogenesis and could be potentially used as predictive or prognostic markers. Cardioproteomic is still in its infancy and relatively few cardiovascular diseases have been investigated. However, it has enormously increased our knowledge of the complexity of the myocardium in terms of protein composition at cellular and organelle levels. The cardiac proteome is further complicated by protein post-translational modifications, which may regulate organelle function in physiological and pathological conditions. Therefore, the incorporation of proteomics into cardiovascular research will provide a means of exploring the mechanisms of disease onset and progression. This will in turn ultimately lead to increased efficiency of diagnosis and/or monitoring of treatment, which could dramatically increase the ability of the clinician to recognize cardiovascular disease states at a relatively early stage, and to improve the therapeutic approach.

摘要

蛋白质组学是对“蛋白质组”的研究,即基因组的全部蛋白质组成。然而,人们已经充分认识到,蛋白质组远比生物学中“一个基因,一种蛋白质”的中心法则所暗示的要复杂得多。蛋白质组包含细胞或生物体在特定时间的所有蛋白质,不仅包括直接从遗传信息翻译而来的蛋白质,还包括转录本的可变剪接和翻译后加工产生的一系列修饰蛋白质,这些修饰有可能改变蛋白质的结构或生物学功能。由于蛋白质几乎参与了每一种细胞功能,控制着每一种调节机制,并且在疾病状态下会发生修饰,蛋白质组决定了细胞的表型,进而决定了细胞所构成的组织或器官的表型。这导致了蛋白质表达和修饰的动态、持续过程。因此,蛋白质组由来自蛋白质表达、翻译后修饰、加工和周转、定位以及时间的信息组成。蛋白质组学旨在识别和表征这些蛋白质变化,如果应用于心血管科学领域,它有可能揭示那些与发病机制相关的蛋白质,并有可能用作预测或预后标志物。心脏蛋白质组学仍处于起步阶段,对相对较少的心血管疾病进行了研究。然而,它极大地增加了我们在细胞和细胞器水平上对心肌蛋白质组成复杂性的认识。蛋白质翻译后修饰使心脏蛋白质组更加复杂,这些修饰可能在生理和病理条件下调节细胞器功能。因此,将蛋白质组学纳入心血管研究将提供一种探索疾病发生和发展机制的方法。这反过来最终将提高诊断和/或治疗监测的效率,这可能会显著提高临床医生在相对早期识别心血管疾病状态的能力,并改善治疗方法。

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