Full Text:   <2678>

Summary:  <1663>

Suppl. Mater.: 

CLC number: 

On-line Access: 2021-09-10

Received: 2020-11-16

Revision Accepted: 2021-02-21

Crosschecked: 0000-00-00

Cited: 0

Clicked: 3931

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Yuehong ZHENG

https://orcid.org/0000-0002-0704-5469

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.9 P.733-745

http://doi.org/10.1631/jzus.B2000713


Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics


Author(s):  Lei JI, Siliang CHEN, Guangchao GU, Wei WANG, Jinrui REN, Fang XU, Fangda LI, Jianqiang WU, Dan YANG, Yuehong ZHENG

Affiliation(s):  Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; more

Corresponding email(s):   yuehongzheng@yahoo.com

Key Words:  Abdominal aortic aneurysm (AAA), Atherosclerosis (AS), Untargeted metabolomics, Transcriptomics


Lei JI, Siliang CHEN, Guangchao GU, Wei WANG, Jinrui REN, Fang XU, Fangda LI, Jianqiang WU, Dan YANG, Yuehong ZHENG. Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics[J]. Journal of Zhejiang University Science B, 2021, 22(9): 733-745.

@article{title="Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics",
author="Lei JI, Siliang CHEN, Guangchao GU, Wei WANG, Jinrui REN, Fang XU, Fangda LI, Jianqiang WU, Dan YANG, Yuehong ZHENG",
journal="Journal of Zhejiang University Science B",
volume="22",
number="9",
pages="733-745",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000713"
}

%0 Journal Article
%T Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics
%A Lei JI
%A Siliang CHEN
%A Guangchao GU
%A Wei WANG
%A Jinrui REN
%A Fang XU
%A Fangda LI
%A Jianqiang WU
%A Dan YANG
%A Yuehong ZHENG
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 9
%P 733-745
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000713

TY - JOUR
T1 - Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics
A1 - Lei JI
A1 - Siliang CHEN
A1 - Guangchao GU
A1 - Wei WANG
A1 - Jinrui REN
A1 - Fang XU
A1 - Fangda LI
A1 - Jianqiang WU
A1 - Dan YANG
A1 - Yuehong ZHENG
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 9
SP - 733
EP - 745
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000713


Abstract: 
abdominal aortic aneurysm (AAA) and atherosclerosis (AS) have considerable similarities in clinical risk factors and molecular pathogenesis. The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics, and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics. Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry (LC-MS). A total of 18 remarkably different metabolites were identified, and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS, with an area under the curve (AUC) of 0.93. Subsequently, we analyzed both the metabolomics and transcriptomics data and found that seven metabolites, especially 2'-deoxy-D-ribose (2dDR), were significantly correlated with differentially expressed genes. In conclusion, our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients, and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.

通过非靶向代谢组学和转录组学发现人动脉粥样硬化性腹主动脉瘤的潜在生物标志物

目的:腹主动脉瘤(AAA)和动脉粥样硬化(AS)在临床危险因素和分子发病机制上有相当大的相似之处。我们的研究旨在从代谢组学的角度研究AAA和AS之间的差异,并通过与转录组学的整合分析探索差异代谢物的潜在机制。
创新点:从代谢组学的角度探究了AAA和AS之间的差异;采用关联分析,探究差异代谢物和差异基因的交互作用整合了代谢组学和转录组学。
方法:应用32例AAA和32例AS患者的血浆样本表征代谢物谱,采用非靶向液相色谱质谱法(LC-MS),探究AAA与AS之间代谢物水平的差异;应用GEO数据集GSE57691,探究AAA与AS之间基因表达的差异;最后应用Spearman相关分析探究差异代谢物与差异基因之间的相关性。
结论:本研究共鉴定出18种显著差异代谢物,其中7种代谢物的组合可能作为区分AAA和AS的生物标志物,曲线下面积(AUC)为0.93。通过整合代谢组学和转录组学数据,发现这7种代谢物,尤其是2’-脱氧-D-核糖(2dDR)与差异表达基因显著相关。本研究提供了AAA和AS患者血浆代谢物的全面概况,并为动脉粥样硬化性AAA的发病机制提供了研究方向。

关键词:腹主动脉瘤(AAA);动脉粥样硬化(AS);非靶向代谢组学;转录组学

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AlcornHG, WolfsonSK, Sutton-TyrrellK, et al., 1996. Risk factors for abdominal aortic aneurysms in older adults enrolled in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol, 16(8):963-970.

[2]ArdestaniA, YazdanparastR, NejadAS, 2008. 2-Deoxy-D-ribose-induced oxidative stress causes apoptosis in human monocytic cells: prevention by pyridoxal-5'-phosphate. Toxicol in Vitro, 22(4):968-979.

[3]BirosE, GäbelG, MoranCS, et al., 2015. Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease. Oncotarget, 6(15):12984-12996.

[4]BradleyDT, HughesAE, BadgerSA, et al., 2013. A variant in LDLR is associated with abdominal aortic aneurysm. Circ Cardiovasc Genet, 6(5):498-504.

[5]CornuzJ, Sidoti PintoC, TevaearaiH, et al., 2004. Risk factors for asymptomatic abdominal aortic aneurysm: systematic review and meta-analysis of population-based screening studies. Eur J Public Health, 14(4):343-349.

[6]DikiciS, BullockAJ, YarM, et al., 2020. 2-Deoxy-D-ribose (2dDR) upregulates vascular endothelial growth factor (VEGF) and stimulates angiogenesis. Microvasc Res, 131:104035.

[7]DunnWB, BroadhurstD, BegleyP, et al., 2011. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc, 6(7):1060-1083.

[8]FerraraN, WinerJ, BurtonT, 1991. Aortic smooth muscle cells express and secrete vascular endothelial growth factor. Growth Factors, 5(2):141-148.

[9]FicoA, ManganelliG, CiglianoL, et al., 2008. 2-Deoxy-D-ribose induces apoptosis by inhibiting the synthesis and increasing the efflux of glutathione. Free Radic Biol Med, 45(2):211-217.

[10]GanSJ, YeB, QianSX, et al., 2015. Immune- and ribosome-related genes were associated with systemic vasculitis. Scand J Immunol, 81(2):96-101.

[11]GolledgeJ, NormanPE, 2010. Atherosclerosis and abdominal aortic aneurysm: cause, response, or common risk factors? Arterioscler Thromb Vasc Biol, 30(6):1075-1077.

[12]HaraguchiM, MiyaderaK, UemuraK, et al., 1994. Angiogenic activity of enzymes. Nature, 368(6468):198.

[13]HaringB, SelvinE, HeXT, et al., 2018. Adherence to the dietary approaches to stop hypertension dietary pattern and risk of abdominal aortic aneurysm: results from the ARIC study. J Am Heart Assoc, 7(21):e009340.

[14]HarrisonSC, SmithAJP, JonesGT, et al., 2013. Interleukin-6 receptor pathways in abdominal aortic aneurysm. Eur Heart J, 34(48):3707-3716.

[15]ItoS, AkutsuK, TamoriY, et al., 2008. Differences in atherosclerotic profiles between patients with thoracic and abdominal aortic aneurysms. Am J Cardiol, 101(5):696-699.

[16]JiL, ChenSL, GuGC, et al., 2021. Exploration of crucial mediators for carotid atherosclerosis pathogenesis through integration of microbiome, metabolome, and transcriptome. Front Physiol, 12:645212.

[17]JohnsonCH, IvanisevicJ, SiuzdakG, 2016. Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol, 17(7):451-459.

[18]JonesGT, BownMJ, GretarsdottirS, et al., 2013. A sequence variant associated with sortilin-1 (SORT1) on 1p13.3 is independently associated with abdominal aortic aneurysm. Hum Mol Genet, 22(14):2941-2947.

[19]KaluzaJ, StackelbergO, HarrisHR, et al., 2019. Anti-inflammatory diet and risk of abdominal aortic aneurysm in two Swedish cohorts. Heart, 105(24):1876-1883.

[20]KentKC, 2014. Abdominal aortic aneurysms. N Engl J Med, 371(22):2101-2108.

[21]KimK, ZakharkinSO, AllisonDB, 2010. Expectations, validity, and reality in gene expression profiling. J Clin Epidemiol, 63(9):950-959.

[22]KnoxAJ, CorbettL, StocksJ, et al., 2001. Human airway smooth muscle cells secrete vascular endothelial growth factor: up-regulation by bradykinin via a protein kinase C and prostanoid-dependent mechanism. FASEB J, 15(13):2480-2488.

[23]LeeperNJ, RaiesdanaA, KojimaY, et al., 2013. Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation. Arterioscler Thromb Vasc Biol, 33(1):e1-e10.

[24]LiXS, WangZN, CajkaT, et al., 2018. Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk. JCI Insight, 3(6):e99096.

[25]Lindquist LiljeqvistM, HultgrenR, BergmanO, et al., 2020. Tunica-specific transcriptome of abdominal aortic aneurysm and the effect of intraluminal thrombus, smoking, and diameter growth rate. Arterioscler Thromb Vasc Biol, 40(11):2700-2713.

[26]MaXH, YaoHR, YangYH, et al., 2018. miR-195 suppresses abdominal aortic aneurysm through the TNF-α/NF-κB and VEGF/PI3K/Akt pathway. Int J Mol Med, 41(4):2350-2358.

[27]MacelM, van DamNM, KeurentjesJJB, 2010. Metabolomics: the chemistry between ecology and genetics. Mol Ecol Resour, 10(4):583-593.

[28]MoxonJV, LiuDW, WongG, et al., 2014. Comparison of the serum lipidome in patients with abdominal aortic aneurysm and peripheral artery disease. Circ Cardiovasc Genet, 7(1):71-79.

[29]MurakamiM, IwaiS, HiratsukaS, et al., 2006. Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocytes/macrophages. Blood, 108(6):1849-1856.

[30]NASCET (North American Symptomatic Carotid Endarterectomy Trial) collaborators, 1991. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med, 325(7):445-453.

[31]NingXJ, DingN, BallewSH, et al., 2020. Diabetes, its duration, and the long-term risk of abdominal aortic aneurysm: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis, 313:137-143.

[32]Ofir-RosenfeldY, BoggsK, MichaelD, et al., 2008. Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26. Mol Cell, 32(2):180-189.

[33]PalazzuoliA, GallottaM, GuerrieriG, et al., 2008. Prevalence of risk factors, coronary and systemic atherosclerosis in abdominal aortic aneurysm: comparison with high cardiovascular risk population. Vasc Health Risk Manag, 4(4):877-883.

[34]PearceWH, ShivelyVP, 2006. Abdominal aortic aneurysm as a complex multifactorial disease: interactions of polymorphisms of inflammatory genes, features of autoimmunity, and current status of MMPs. Ann N Y Acad Sci, 1085(1):117-132.

[35]QureshiMI, GrecoM, VorkasPA, et al., 2017. Application of metabolic profiling to abdominal aortic aneurysm research. J Proteome Res, 16(7):2325-2332.

[36]Schrimpe-RutledgeAC, CodreanuSG, SherrodSD, et al., 2016. Untargeted metabolomics strategies-challenges and emerging directions. J Am Soc Mass Spectrom, 27(12):1897-1905.

[37]ShannonP, MarkielA, OzierO, et al., 2003. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res, 13(11):2498-2504.

[38]SharmaR, RamanathanA, 2020. The aging metabolome-biomarkers to hub metabolites. Proteomics, 20(5-6):1800407.

[39]SpitlerKM, DaviesBSJ, 2020. Aging and plasma triglyceride metabolism. J Lipid Res, 61(8):1161-1167.

[40]Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, et al., 1991. Suggested standards for reporting on arterial aneurysms. J Vasc Surg, 13(3):452-458.

[41]TakagiM, AbsalonMJ, McLureKG, et al., 2005. Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell, 123(1):49-63.

[42]UcuzianAA, GassmanAA, EastAT, et al., 2010. Molecular mediators of angiogenesis. J Burn Care Res, 31(1):158-175.

[43]UfnalM, ZadloA, OstaszewskiR, 2015. TMAO: a small molecule of great expectations. Nutrition, 31(11-12):1317-1323.

[44]US Preventive Services Task Force, 2019. Screening for abdominal aortic aneurysm: US Preventive Services Task Force Recommendation Statement. JAMA, 322(22):2211-2218.

[45]UssherJR, ElmariahS, GersztenRE, et al., 2016. The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease. J Am Coll Cardiol, 68(25):2850-2870.

[46]van HoveAH, BenoitDSW, 2015. Depot-based delivery systems for pro-angiogenic peptides: a review. Front Bioeng Biotechnol, 3:102.

[47]WassefM, BaxterBT, ChisholmRL, et al., 2001. Pathogenesis of abdominal aortic aneurysms: a multidisciplinary research program supported by the National Heart, Lung, and Blood Institute. J Vasc Surg, 34(4):730-738.

[48]XuBH, IidaY, GloverKJ, et al., 2019. Inhibition of VEGF (vascular endothelial growth factor)-A or its receptor activity suppresses experimental aneurysm progression in the aortic elastase infusion model. Arterioscler Thromb Vasc Biol, 39(8):1652-1666.

[49]ZampieriM, SekarK, ZamboniN, et al., 2017. Frontiers of high-throughput metabolomics. Curr Opin Chem Biol, 36:15-23.

[50]ZannasAS, JiaMW, HafnerK, et al., 2019. Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB-driven inflammation and cardiovascular risk. Proc Natl Acad Sci USA, 116(23):11370-11379.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE