基努瑞宁通路的新陈代谢随着临床前和结核病相关的肺动脉高血压的发展而演变
Catherine E Simpson1, Anjira S Ambade1, Robert Harlan2
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
涉及kynurenine通路的代谢变化在患有肺动脉高血压 (PAH) 的全身性硬化症患者的早期增加. 这种与TDO2基因表达相关的代谢转变在诊断之前发生,并预测疾病的严重程度和存活率.
科学领域:
- 代谢学 代谢学 代谢学
- 肺动脉高血压的病理生理学
- 生物标志物发现发现
背景情况:
- 肺动脉高血压 (PAH) 的发展尚不清楚.
- 系统性硬化症 (SSc) 患者进行PAH查,提供了一个独特的队列来研究早期代谢变化.
- 识别早期的代谢变化可以揭示PAH的生物标志物和治疗点.
研究的目的:
- 在SSc患者中研究PAH发育期间的代谢演变.
- 为了确定早期的代谢生物标志物预测SSc-PAH.
- 探索金氨酸通路和TDO2在PAH病变发生过程中的作用.
主要方法:
- 长度血清代谢使用质谱在SSc患者和没有PAH.
- 在第二个队列和临床前PAH模型中验证.
- 代谢物水平与临床,血液动力学和基因表达数据的相关性 (TDO2).
主要成果:
- 在患有PAH的SSc患者中观察到增加的kynurenine与triptophan比率 (kyn/trp).
- 较高的kyn/trp水平预测了SSc-PAH诊断和死亡率.
- 在人类和动物模型中,上调的金氨酸途径代谢和TDO2基因表达与PAH严重程度相关.
结论:
- 在SSc队列中,在PAH发育过程中发生了kynurenine通路的早期上调.
- kynurenine路径代谢物是PAH的潜在早期生物标志物.
- TDO2是PAH的潜在治疗标.
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