Interstage Single Ventricle Heart Disease Infants Show Dysregulation in Multiple Metabolic Pathways: Targeted Metabolomics Analysis.
Interstage Single Ventricle Heart Disease Infants Show Dysregulation in Multiple Metabolic Pathways: Targeted Metabolomics Analysis.
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DOI：
10.1016/j.jacadv.2022.100169
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发表时间：
2023-01-01
期刊：
影响因子：
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通讯作者：
Davidson, Jesse A
中科院分区：
文献类型：
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作者：
Frank, Benjamin S;Khailova, Ludmila;Davidson, Jesse A
背景：患有 SVHD 的婴儿会经历与肺血管功能不全相关的发病。代谢组学分析涉及系统生物学方法来识别复杂疾病中的新生物标志物和途径。 SVHD 婴儿的代谢组尚不清楚，之前也没有研究评估血清代谢模式与分期 SVHD 姑息治疗的肺血管准备情况之间的关系。 目的：本研究的目的是评估单心室心脏病 (SVHD) 间期婴儿的循环代谢组，并确定代谢物水平是否与肺血管功能不全相关。 方法：这是一项前瞻性队列研究，纳入了 52 名患有 SVHD 的婴儿。正在接受第二阶段姑息治疗的 SVHD 和 48 名健康婴儿。通过串联质谱法对 SVHD 第 2 阶段前、第 2 阶段后和对照血清样本进行靶向代谢组表型分析（175 种代谢物）。从病历中提取临床变量。结果：随机森林分析很容易区分病例和对照以及术前和术后样本。 175 种代谢物中有 74 种在 SVHD 和对照组之间存在差异。 39 条代谢途径中有 27 条发生改变，包括磷酸戊糖和精氨酸代谢。 SVHD 患者在不同时间点的 71 种代谢物存在差异。 39 条通路中的 33 条在术后发生了改变，包括精氨酸和色氨酸代谢。我们发现肺血管阻力较高的患者术前蛋氨酸代谢物有增加的趋势，术后低氧血症较严重的患者术后色氨酸代谢物有较高的趋势。结论：阶段性 SVHD 婴儿的循环代谢组与对照组显着不同，并且在第 2 阶段后进一步扰乱。一些代谢物显示出与不良结局相关的趋势。代谢失调可能是早期 SVHD 病理学的一个重要因素。
BACKGROUND: Infants with SVHD experience morbidity related to pulmonary vascular inadequacy. Metabolomic analysis involves a systems biology approach to identifying novel biomarkers and pathways in complex diseases. The metabolome of infants with SVHD is not well understood and no prior study has evaluated the relationship between serum metabolite patterns and pulmonary vascular readiness for staged SVHD palliation.OBJECTIVES: The purpose of this study was to evaluate the circulating metabolome of interstage infants with single ventricle heart disease (SVHD) and determine whether metabolite levels were associated with pulmonary vascular inadequacy.METHODS: This was a prospective cohort study of 52 infants with SVHD undergoing Stage 2 palliation and 48 healthy infants. Targeted metabolomic phenotyping (175 metabolites) was performed by tandem mass spectrometry on SVHD pre-Stage 2, post-Stage 2, and control serum samples. Clinical variables were extracted from the medical record.RESULTS: Random forest analysis readily distinguished between cases and controls and preoperative and postoperative samples. Seventy-four of 175 metabolites differed between SVHD and controls. Twenty-seven of 39 metabolic pathways were altered including pentose phosphate and arginine metabolism. Seventy-one metabolites differed in SVHD patients between timepoints. Thirty-three of 39 pathways were altered postoperatively including arginine and tryptophan metabolism. We found trends toward increased preoperative methionine metabolites in patients with higher pulmonary vascular resistance and higher postoperative tryptophan metabolites in patients with greater postoperative hypoxemia.CONCLUSIONS: The circulating metabolome of interstage SVHD infants differs significantly from controls and is further disrupted after Stage 2. Several metabolites showed trends toward association with adverse outcomes. Metabolic dysregulation may be an important factor in early SVHD pathobiology.