CLC number:
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 0000-00-00
Cited: 0
Clicked: 4535
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.
[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>