Cytokine profiling in pulmonary arterial hypertension: the role of redox homeostasis and sex.
Cytokine profiling in pulmonary arterial hypertension: the role of redox homeostasis and sex.
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DOI：
10.1016/j.trsl.2022.03.013
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发表时间：
2022-09
影响因子：
7.8
通讯作者：
Rafikova, Olga
中科院分区：
文献类型：
--
作者：
Rafikov, Ruslan;Rischard, Franz;Vasilyev, Mikhail;Varghese, Mathews V.;Yuan, Jason X-J;Desai, Ankit A.;Garcia, Joe G. N.;Rafikova, Olga
肺动脉高压（PAH）是一种致命的疾病，具有明确的性别二态性。激活的炎症反应和改变的氧化还原稳态均以性别特异性方式表现，与 PAH 发展的致病机制有关。本研究旨在评估性别和血浆氧化还原状态对循环细胞因子谱的影响。血浆氧化还原电位 (ORP) 作为氧化还原状态的替代指标，在男性和女性 1 组 PAH 以及健康受试者中进行了分析。对 2 个 PAH 组中 27 种循环细胞因子的概况进行比较，显示血浆 ORP 的最高和最低四分位数，与临床参数相关，并用于预测患者生存。对 ORP 最高和最低的 PAH 组的分析揭示了女性细胞因子水平升高与氧化应激增加之间的相关性。相反，在男性中，细胞因子表达在较低氧化环境中增加（IL-1b 除外）。细胞因子表达增加与 PAH 严重程度的相关性高度依赖于性别，对应于男性 PAH 严重程度的增加和女性 PAH 严重程度的减轻。根据细胞因子和氧化还原组合数据进行训练的机器学习算法可以以 80% 的准确度预测 PAH 死亡率。我们的结论是，PAH 患者循环细胞因子的分布具有氧化还原和性别依赖性，这表明迫切需要对接受抗炎治疗的患者群体进行分层。联合细胞因子和/或氧化还原分析显示出预测患者生存的有希望的价值。
Pulmonary arterial hypertension (PAH) is a fatal disease with a well-established sexual dimorphism. Activated inflammatory response and altered redox homeostasis, both known to manifest in a sex-specific manner, are implicated in the pathogenic mechanisms involved in PAH development. This study aimed to evaluate the impact of sex and plasma redox status on circulating cytokine profiles. Plasma oxidation-reduction potential (ORP), as a substitute measure of redox status, was analyzed in male and female Group 1 PAH and healthy subjects. The profiles of 27 circulating cytokines were compared in 2 PAH groups exhibiting the highest and lowest quartile for plasma ORP, correlated with clinical parameters, and used to predict patient survival. The analysis of the PAH groups with the highest and lowest ORP revealed a correlation between elevated cytokine levels and increased oxidative stress in females. In contrast, in males, cytokine expressions were increased in the lower oxidative environment (except for IL-1b). Correlations of the increased cytokine expressions with PAH severity were highly sex-dependent and corresponded to the increase in PAH severity in males and less severe PAH in females. Machine learning algorithms trained on the combined cytokine and redox profiles allowed the prediction of PAH mortality with 80% accuracy. We conclude that the profile of circulating cytokines in PAH patients is redox- and sex-dependent, suggesting the vital need to stratify the patient cohort subjected to anti-inflammatory therapies. Combined cytokine and/or redox profiling showed promising value for predicting the patients' survival.
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影响因子：
4.9
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