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通过多组学分析鉴定肥胖中主动脉疾病的血清生物标志物和治疗靶点。

Identification of serum biomarkers and therapeutic targets for aortic diseases in obesity through multi-omics analysis.

作者信息

Wang Tianren, Wang Yuhang, Wang Yansong, Wang Xiaokang, Cheng Xinyu, Tan Qiwen, Zhu Tiancheng, Teng Xiaomei, Huang Haoyue, Shen Zhenya

机构信息

Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Institute for Cardiovascular Science, Soochow University, Suzhou, China.

出版信息

J Thorac Dis. 2024 Dec 31;16(12):8435-8449. doi: 10.21037/jtd-24-1113. Epub 2024 Dec 28.

Abstract

BACKGROUND

Obesity is associated with an increased risk of aortic diseases and operative risks. Currently, there are no effective drugs available to prevent the occurrence and progression of aortic aneurysms or dissections. We investigated potential biomarkers and therapeutic targets using a multi-omics approach.

METHODS

Clinical data from 237 patients with aortic disease were analyzed based on body mass index (BMI) to explore the relationship between BMI and clinical outcomes. An obesity mouse model was developed by feeding a high fat diet (HFD), and an aortic disease model was established by administering human angiotensin II (AngII) at a dosage of 1,000 ng/min/kg via osmotic minipumps. Through analysis of murine aortic transcriptomics and serum proteomics, we identified potential biomarkers for aortic disease with obesity. Enzyme-linked immunosorbent assay was used to detect these biomarkers in human serum.

RESULTS

This study analyzed a cohort of 237 patients with aortic disease and 72 patients with valvulopathy. Patients with aortic disease exhibited a significantly higher BMI and a lower mean age compared to those with valvulopathy. Among the aortic disease group, elevated BMI was associated with a younger age, increased systolic and diastolic blood pressure, and a higher percentage of neutrophils. Transcriptomic analysis revealed an enrichment of genes related to complement and coagulation cascades, as well as the prion disease pathway. Proteomic analysis showed an enrichment of proteins associated with African trypanosomiasis and the estrogen signaling pathway. By integrating transcriptomic and proteomic profiles, complement component 5 (C5) and apolipoprotein D (apoD) were identified as potential biomarkers for the adverse effects of obesity.

CONCLUSIONS

High BMI is associated with an increased risk of aortic disease, particularly aortic dissection. Serum C5 and apoD have been identified as potential biomarkers for evaluating the risk of aortic disease in obese individuals. Further research is necessary to explore the pathophysiological pathways correlated with these biomarkers and their potential clinical applications.

摘要

背景

肥胖与主动脉疾病风险增加及手术风险相关。目前,尚无有效药物可预防主动脉瘤或夹层的发生与进展。我们采用多组学方法研究潜在的生物标志物和治疗靶点。

方法

基于体重指数(BMI)分析237例主动脉疾病患者的临床数据,以探讨BMI与临床结局之间的关系。通过喂食高脂饮食(HFD)建立肥胖小鼠模型,并通过渗透微型泵以1000 ng/min/kg的剂量给予人血管紧张素II(AngII)建立主动脉疾病模型。通过对小鼠主动脉转录组学和血清蛋白质组学的分析,我们确定了肥胖相关主动脉疾病的潜在生物标志物。采用酶联免疫吸附测定法检测人血清中的这些生物标志物。

结果

本研究分析了237例主动脉疾病患者和72例瓣膜病患者。与瓣膜病患者相比,主动脉疾病患者的BMI显著更高,平均年龄更低。在主动脉疾病组中,BMI升高与年龄较小、收缩压和舒张压升高以及中性粒细胞百分比更高有关。转录组分析显示与补体和凝血级联以及朊病毒疾病途径相关的基因富集。蛋白质组分析显示与非洲锥虫病和雌激素信号通路相关的蛋白质富集。通过整合转录组和蛋白质组图谱,补体成分5(C5)和载脂蛋白D(apoD)被确定为肥胖不良影响的潜在生物标志物。

结论

高BMI与主动脉疾病风险增加相关,尤其是主动脉夹层。血清C5和apoD已被确定为评估肥胖个体主动脉疾病风险的潜在生物标志物。有必要进一步研究探索与这些生物标志物相关的病理生理途径及其潜在的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e7/11740044/5e4efce7ba25/jtd-16-12-8435-f1.jpg

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