Probing nitric oxide signaling using molecular MRI.

Probing nitric oxide signaling using molecular MRI.
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DOI:
10.1016/j.freeradbiomed.2022.08.042
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发表时间:
2022-10
影响因子:
7.4
通讯作者:
Jasanoff A
Jasanoff A
中科院分区:
医学1区
文献类型:
--
作者:
Barandov A;Ghosh S;Jasanoff A

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对一氧化氮(NO)信号的广泛测量可以帮助理解和诊断NO在其中发挥关键作用的许多生理过程。如果配备了对NO和NO相关靶敏感的分子探针,磁共振成像(MRI)可以为这一目的提供特别强大的方法。在这篇综述中,我们讨论了MRI可检测的探针的发展,这些探针可以在动物和潜在的人类受试者中研究氮能信号。主要的探针家族包括用于直接捕获和报告整合的NO水平的造影剂,以及响应或模拟一氧化氮合酶活性的分子。对于每一组,我们概述了相关的分子机制,并讨论了在体外和动物中获得的结果。迄今为止描述的最有希望的活体数据是通过使用基于NO捕捉的松弛剂和使用工程一氧化氮合酶获得的,这些一氧化氮合酶提供了NO信号通路激活的血流动力学读数。这些进展为不断努力提高NO相关分子磁共振技术的敏感性、特异性和临床适用性奠定了滩头阵地。
Wide field measurements of nitric oxide (NO) signaling could help understand and diagnose the many physiological processes in which NO plays a key role. Magnetic resonance imaging (MRI) can support particularly powerful approaches for this purpose if equipped with molecular probes sensitized to NO and NO-associated targets. In this review, we discuss the development of MRI-detectable probes that could enable studies of nitrergic signaling in animals and potentially human subjects. Major families of probes include contrast agents designed to capture and report integrated NO levels directly, as well as molecules that respond to or emulate the activity of nitric oxide synthase enzymes. For each group, we outline the relevant molecular mechanisms and discuss results that have been obtained in vitro and in animals. The most promising in vivo data described to date have been acquired using NO capture-based relaxation agents and using engineered nitric oxide synthases that provide hemodynamic readouts of NO signaling pathway activation. These advances establish a beachhead for ongoing efforts to improve the sensitivity, specificity, and clinical applicability of NO-related molecular MRI technology.
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