心血管健康和疾病中的氧化还原信号和氧化还原生物标志物。

Yasmin Sultana, Damanpreet Kaur Lang, Thomson Santosh Alex, Rakhi Khabiya, Akanksha Dwivedi, Saikat Sen, Raja Chakraborty
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引用次数: 0

摘要

活性氮和活性氧(RNS 和 ROS)的过度产生与糖尿病、高血压、高脂血症、中风、心绞痛和其他心血管疾病的发病机制有关。这些物质部分由线粒体呼吸链、NADPH 氧化酶和黄嘌呤氧化酶产生。RNS 和 ROS 都会导致氧化应激,而氧化应激是心血管疾病发生的必要条件。除了羟基离子、过氧化氢和超氧阴离子等 ROS 物种外,一氧化氮、过硫酸、过亚硝酸和二氧化氮自由基等 RNS 物种也与多种心血管疾病有关。它们会促进内皮功能障碍、血管炎症、脂质过氧化和氧化损伤,所有这些都会导致心血管疾病的发生。了解导致 RNS 和 ROS 产生的机制对于确定潜在的治疗目标至关重要。氧化还原生物标志物是氧化应激的指标,是诊断和预测心血管状态的重要工具。蛋白质组学、代谢组学、基因组学和转录组学的进步使得识别和检测这些小分子成为可能。以下氧化还原生物标记物就是显著的例子:例如 3-硝基酪氨酸、4-羟基-2-壬烯醛、8-异前列腺素 F2、8-羟基-2-脱氧鸟苷、丙二醛、Diacron 活性氧代谢物、总硫醇和特定的 microRNA(如 miRNA199、miRNA21、miRNA1254、miRNA1306-5p、miRNA26b-5p 和 miRNA660-5p)。尽管氧化还原生物标志物具有巨大的潜力,但其临床应用却面临着挑战。氧化还原生物标志物的半衰期通常较短,在血液中的含量也较少,因此对它们的识别和测量具有挑战性。对生物标志物数据的解释也可能受到混杂因素和各种氧化应激途径复杂相互作用的影响。因此,需要进行深入的验证研究并开发灵敏、精确的检测方法来解决这些问题。在寻找氧化还原生物标记物的过程中,应用了质谱、免疫测定和分子诊断等尖端技术。新的平台和技术使准确检测和监测氧化还原生物标志物成为可能,从而促进了它们在临床环境中的应用。我们对参与心血管疾病的 RNS 和 ROS 的认识不断扩大,这使得开发氧化还原生物标记物作为诊断和预后工具成为可能。克服与这些生物标志物的应用相关的挑战,利用先进的检测技术提高它们的临床适用性,最终将有利于心血管疾病的管理和治疗。
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Redox-signalling and Redox Biomarkers in Cardiovascular Health and Disease.

Overproduction of reactive nitrogen and oxygen species (RNS and ROS) has been linked to the pathogenesis of diabetes, hypertension, hyperlipidemia, stroke, angina, and other cardiovascular diseases. These species are produced in part by the mitochondrial respiratory chain, NADPH oxidase, and xanthine oxidase. RNS and ROS both contribute to oxidative stress, which is necessary for the development of cardiovascular disorders. In addition to ROS species like hydroxyl ion, hydrogen peroxide, and superoxide anion, RNS species like nitric oxide, peroxynitrous acid, peroxynitrite, and nitrogen dioxide radicals have also been linked to a number of cardiovascular conditions. They promote endothelial dysfunction, vascular inflammation, lipid peroxidation, and oxidative damage, all of which contribute to the development of cardiovascular pathologies. It's crucial to understand the mechanisms that result in the production of RNS and ROS in order to identify potential therapeutic targets. Redox biomarkers serve as indicators of oxidative stress, making them crucial tools for diagnosing and predicting cardiovascular states. The advancements in proteomics, metabolomics, genomics, and transcriptomics have made the identification and detection of these small molecules possible. The following redox biomarkers are notable examples: 3-nitrotyrosine, 4-hydroxy-2-nonenal, 8- iso-prostaglandin F2, 8-hydroxy-2-deoxyguanosine, malondialdehyde, Diacron reactive oxygen metabolites, total thiol, and specific microRNAs (e.g. miRNA199, miRNA21, miRNA1254, miRNA1306-5p, miRNA26b-5p, and miRNA660-5p) are examples. Although redox biomarkers have great potential, their clinical applicability faces challenges. Redox biomarkers frequently have a short half-life and exist in small quantities in the blood, making them challenging to identify and measure. The interpretation of biomarker data may also be influenced by confounding factors and the complex interplay of various oxidative stress pathways. Therefore, in-depth validation studies and the development of sensitive and precise detection methods are needed to address these problems. In the search for redox biomarkers, cutting-edge techniques like mass spectrometry, immunoassays, and molecular diagnostics are applied. New platforms and technologies have made it possible to accurately detect and monitor redox biomarkers, which facilitates their use in clinical settings. Our expanding knowledge of RNS and ROS involvement in cardiovascular disorders has made it possible to develop redox biomarkers as diagnostic and prognostic tools. Overcoming the challenges associated with their utility and utilizing advanced detection techniques, which will improve their clinical applicability, will ultimately benefit the management and treatment of cardiovascular conditions.

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