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在年轻人群中识别出 6 种心血管风险生物标志物:早期预防的有前途工具。

Identification of six cardiovascular risk biomarkers in the young population: A promising tool for early prevention.

机构信息

Immunoallergy and Proteomics Laboratory, Department of Immunology, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.

Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos SESCAM, Toledo, Spain.

出版信息

Atherosclerosis. 2019 Mar;282:67-74. doi: 10.1016/j.atherosclerosis.2019.01.003. Epub 2019 Jan 14.

Abstract

BACKGROUND AND AIMS

The predictive value of traditional CV risk calculators is limited. Novel indicators of CVD progression are needed particularly in the young population. The main aim of this study was the identification of a molecular profile with added value to classical CV risk estimation.

METHODS

Eighty-one subjects (30-50 years) were classified in 3 groups according to their CV risk: healthy subjects; individuals with CV risk factors; and those who had suffered a previous CV event. The urine proteome was quantitatively analyzed and significantly altered proteins were identified between patients' groups, either related to CV risk or established organ damage. Target-MS and ELISA were used for confirmation in independent patients' cohorts. Systems Biology Analysis (SBA) was carried out to identify functional categories behind CVD.

RESULTS

4309 proteins were identified, 75 of them differentially expressed. ADX, ECP, FETUB, GDF15, GUAD and NOTCH1 compose a fingerprint positively correlating with lifetime risk estimate (LTR QRISK). Best performance ROC curve was obtained when ECP, GDF15 and GUAD were combined (AUC = 0.96). SBA revealed oxidative stress response, dilated cardiomyopathy, signaling by Wnt and proteasome, as main functional processes related to CV risk.

CONCLUSIONS

A novel urinary protein signature is shown, which correlates with CV risk estimation in young individuals. Pending further confirmation, this six-protein-panel could help in CV risk assessment.

摘要

背景与目的

传统心血管风险计算器的预测价值有限。需要新型心血管疾病进展指标,特别是在年轻人群中。本研究的主要目的是确定一种具有附加价值的分子谱,以补充传统心血管风险评估。

方法

根据心血管风险将 81 名(30-50 岁)受试者分为 3 组:健康受试者;有心血管危险因素的个体;以及曾发生过心血管事件的个体。定量分析尿液蛋白质组,在患者组之间鉴定出与心血管风险或已建立的器官损伤相关的显著改变的蛋白质。使用靶向-MS 和 ELISA 在独立的患者队列中进行验证。系统生物学分析(SBA)用于识别 CVD 背后的功能类别。

结果

鉴定出 4309 种蛋白质,其中 75 种表达差异。ADX、ECP、FETUB、GDF15、GUAD 和 NOTCH1 组成一个指纹,与终生风险估计(LTR QRISK)呈正相关。当 ECP、GDF15 和 GUAD 联合使用时,获得最佳性能的 ROC 曲线(AUC=0.96)。SBA 揭示了氧化应激反应、扩张型心肌病、Wnt 和蛋白酶体信号传导,是与心血管风险相关的主要功能过程。

结论

显示了一种新型的尿蛋白特征,与年轻人的心血管风险评估相关。在进一步确认之前,这个六蛋白面板可以帮助评估心血管风险。

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