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一种多模式的方法将乳酸确定为右心室衰竭的中心特征,可以在人体血中检测到
Anna Hemnes1, Niki Fortune1, Katie Simon1
1Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Frontiers in medicine
|September 30, 2024
概括
肺动脉高血压 (PAH) 涉及右心室 (RV) 的代谢变化. 这项研究整合了小鼠和人类的多原子数据,揭示了乳酸盐是PAH中RV功能障碍的潜在生物标志物.
科学领域:
- 心血管生物学 心血管生物学
- 代谢学 代谢学 代谢学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 代谢异常是肺动脉高血压 (PAH) 中右心室 (RV) 功能障碍的标志.
- 以前的研究往往集中在单一的奥米克或路径上,限制了全面的理解.
- 整合多种omics模式为PAH的RV故障提供了更深入的机械洞察力.
研究的目的:
- 为了研究PAH动物模型的失败RV的综合代谢和转录组变化.
- 将来自动物模型的发现转化为来自PAH患者的人类血样本.
- 确定PAH中RV功能障碍的新机理见解和潜在生物标志物.
主要方法:
- 使用了可诱导多西环素的BMPR2突变鼠标模型的RV失败.
- 在小鼠RV组织和人体血上进行了综合代谢和转录组分析.
- 鼠标模型和人类PAH患者血之间的相关发现,在培养心肌细胞中进行了验证.
主要成果:
- 失败的小鼠RVs表现出改变的葡萄糖分解,脂肪酸代谢和TCA循环,与酸盐积累和未激活的谷氨酸分解.
- 在PAH患者中,血数据显示糖解,脂肪酸,TCA循环,以及谷氨酸分解途径基因和代谢物的增加.
- 乳酸是失败的VR和循环中唯一升高的代谢物,培养的心肌细胞显示乳酸生产增加.
结论:
- 由RV心肌细胞产生的乳酸可能会被分泌到循环中,作为PAH中RV功能障碍的潜在生物标志物.
- 这项研究强调了综合多原子方法对于理解PAH病理生理学的有用性.
- 需要进一步研究乳酸盐作为PAH中RV功能障碍的诊断标志物.
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