Smidt Heart Institute, Advanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States.
Physiol Rev. 2024 Jul 1;104(3):931-982. doi: 10.1152/physrev.00026.2023. Epub 2024 Feb 1.
Mass spectrometry-based proteomics is a sophisticated identification tool specializing in portraying protein dynamics at a molecular level. Proteomics provides biologists with a snapshot of context-dependent protein and proteoform expression, structural conformations, dynamic turnover, and protein-protein interactions. Cardiac proteomics can offer a broader and deeper understanding of the molecular mechanisms that underscore cardiovascular disease, and it is foundational to the development of future therapeutic interventions. This review encapsulates the evolution, current technologies, and future perspectives of proteomic-based mass spectrometry as it applies to the study of the heart. Key technological advancements have allowed researchers to study proteomes at a single-cell level and employ robot-assisted automation systems for enhanced sample preparation techniques, and the increase in fidelity of the mass spectrometers has allowed for the unambiguous identification of numerous dynamic posttranslational modifications. Animal models of cardiovascular disease, ranging from early animal experiments to current sophisticated models of heart failure with preserved ejection fraction, have provided the tools to study a challenging organ in the laboratory. Further technological development will pave the way for the implementation of proteomics even closer within the clinical setting, allowing not only scientists but also patients to benefit from an understanding of protein interplay as it relates to cardiac disease physiology.
基于质谱的蛋白质组学是一种复杂的鉴定工具,专门用于描绘分子水平上的蛋白质动态。蛋白质组学为生物学家提供了一幅关于依赖于上下文的蛋白质和蛋白质形式表达、结构构象、动态周转和蛋白质-蛋白质相互作用的快照。心脏蛋白质组学可以更深入地了解心血管疾病背后的分子机制,它是未来治疗干预措施发展的基础。本综述总结了基于蛋白质组学的质谱技术的发展、当前技术和未来展望,以及其在心脏研究中的应用。关键技术进步使研究人员能够在单细胞水平上研究蛋白质组,并采用机器人辅助自动化系统来增强样品制备技术,同时,质谱仪的准确性提高,使许多动态翻译后修饰的鉴定变得更加明确。从早期的动物实验到目前具有保留射血分数的心力衰竭的复杂模型,心血管疾病的动物模型为在实验室中研究这个具有挑战性的器官提供了工具。进一步的技术发展将为在临床环境中更紧密地实施蛋白质组学铺平道路,不仅使科学家,而且使患者也能受益于对与心脏疾病生理学相关的蛋白质相互作用的理解。