1H Nuclear Magnetic Resonance Spectroscopy Reveals Changes in Metabolic Phenotype Associated with Disease Stage in Patients with Chronic Venous Disease.

IF 5.7 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE
Sarah Onida, Hannah J Lees, Richmond Bergner, Joseph Shalhoub, Elaine Holmes, Alun H Davies
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Abstract

Objective: Chronic venous disease (CVD) is a condition presenting a great burden to patients and society, with poorly characterised pathophysiology. Metabolic phenotyping can elucidate mechanisms of disease and identify candidate biomarkers. The aim of this study was to determine differences in the metabolic signature between symptomatic patients with CVD and asymptomatic volunteers using proton nuclear magnetic resonance spectroscopy (1H-NMR).

Methods: This was a prospective case control study of consecutive patients with symptomatic CVD and asymptomatic volunteers recruited from a single centre. Participants underwent clinical assessment, venous duplex ultrasound, and blood and urine sampling. Disease stage was defined according to the Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification. 1H-NMR experiments were performed, with data analysed via multivariable statistical techniques.

Results: A total of 622 participants were recruited, including 517 symptomatic patients with CVD (telangiectasia [C1] 0.6%, varicose veins [C2] 48.5%, swelling [C3] 12.0%, skin changes [C4] 27.7%, healed or active ulceration [C5/6] 11.2%) and 105 asymptomatic participants (no disease [C0] 69.5%, telangiectasia [C1] 29.6%). Multivariable analysis revealed differences between the metabolic profile of the symptomatic CVD and asymptomatic groups, and between CEAP clinical classes in the CVD group. Serum aromatic amino acids positively correlated with increasing CEAP clinical class (p < .001). Urinary formate, creatinine, glycine, citrate, succinate, pyruvate, and 2-hydroxyisobutyrate negatively correlated with increasing CEAP clinical class (p < .001). These metabolites are involved in the tricarboxylic acid cycle, hypoxia inducible factor pathway, and one carbon metabolism.

Conclusion: Untargeted biofluid analysis via 1H-NMR has detected metabolites associated with the presence and severity of CVD, highlighting biological pathways of relevance and providing candidate biomarkers to explore in future research.

1H 核磁共振波谱显示慢性静脉疾病患者的代谢表型变化与疾病分期有关。
目的:慢性静脉疾病(CVD)是一种给患者和社会带来巨大负担的疾病,其病理生理学特征不甚明了。代谢表型分析可以阐明疾病机制并确定候选生物标记物。本研究的目的是利用质子核磁共振波谱(1H-NMR)确定有症状的心血管疾病患者与无症状志愿者之间代谢特征的差异:这是一项前瞻性病例对照研究,研究对象是从一个中心连续招募的无症状心血管疾病患者和无症状志愿者。参与者接受了临床评估、静脉双相超声检查以及血液和尿液采样。疾病分期根据临床-病因-解剖-病理生理学(CEAP)分类法进行定义。进行了 1H-NMR 实验,并通过多元统计技术对数据进行了分析:共招募了 622 名参与者,包括 517 名有症状的心血管疾病患者(毛细血管扩张 [C1] 0.6%、静脉曲张 [C2] 48.5%、肿胀 [C3] 12.0%、皮肤变化 [C4] 27.7%、愈合或活动性溃疡 [C5/6] 11.2%)和 105 名无症状参与者(无疾病 [C0] 69.5%、毛细血管扩张 [C1] 29.6%)。多变量分析显示,有症状的心血管疾病组和无症状组之间的代谢概况存在差异,心血管疾病组的 CEAP 临床分级也存在差异。血清芳香族氨基酸与 CEAP 临床分级的增加呈正相关(p < .001)。尿甲酸盐、肌酐、甘氨酸、柠檬酸盐、琥珀酸盐、丙酮酸盐和 2-羟基异丁酸盐与 CEAP 临床分级的增加呈负相关(p < .001)。这些代谢物参与了三羧酸循环、缺氧诱导因子途径和一碳代谢:结论:通过 1H-NMR 进行的非靶向生物流体分析检测出了与心血管疾病的存在和严重程度相关的代谢物,突出了相关的生物通路,并为今后的研究提供了候选生物标记物。
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来源期刊
CiteScore
6.80
自引率
15.80%
发文量
471
审稿时长
66 days
期刊介绍: The European Journal of Vascular and Endovascular Surgery is aimed primarily at vascular surgeons dealing with patients with arterial, venous and lymphatic diseases. Contributions are included on the diagnosis, investigation and management of these vascular disorders. Papers that consider the technical aspects of vascular surgery are encouraged, and the journal includes invited state-of-the-art articles. Reflecting the increasing importance of endovascular techniques in the management of vascular diseases and the value of closer collaboration between the vascular surgeon and the vascular radiologist, the journal has now extended its scope to encompass the growing number of contributions from this exciting field. Articles describing endovascular method and their critical evaluation are included, as well as reports on the emerging technology associated with this field.
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