Plasma and urine metabolomic analyses in aortic valve stenosis reveal shared and biofluid-specific changes in metabolite levels

被引:6
作者
Al Hageh, Cynthia [1 ,2 ]
Rahy, Ryan [2 ]
Khazen, Georges [2 ]
Brial, Francois [1 ]
Khnayzer, Rony S. [2 ]
Gauguier, Dominique [1 ,3 ,4 ]
Zalloua, Pierre A. [5 ]
机构
[1] Univ Paris, INSERM, UMRS 1124, Paris, France
[2] Lebanese Amer Univ, Sch Arts & Sci, Dept Nat Sci, Beirut, Lebanon
[3] McGill Univ, Montreal, PQ, Canada
[4] Genome Quebec Innovat Ctr, Montreal, PQ, Canada
[5] Univ Balamand, Sch Med, Amioun, Lebanon
关键词
CORONARY-HEART-DISEASE; DIETARY FATTY-ACIDS; ARTERY-DISEASE; MYRISTIC ACID; RISK; INDIVIDUALS; POPULATION; MORTALITY; DISCOVERY; DIAGNOSIS;
D O I
10.1371/journal.pone.0242019
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Aortic valve stenosis (AVS) is a prevalent condition among the elderly population that eventually requires aortic valve replacement. The lack of reliable biomarkers for AVS poses a challenge for its early diagnosis and the application of preventive measures. Untargeted gas chromatography mass spectrometry (GC-MS) metabolomics was applied in 46 AVS cases and 46 controls to identify plasma and urine metabolites underlying AVS risk. Multivariate data analyses were performed on pre-processed data (e.g. spectral peak alignment), in order to detect changes in metabolite levels in AVS patients and to evaluate their performance in group separation and sensitivity of AVS prediction, followed by regression analyses to test for their association with AVS. Through untargeted analysis of 190 urine and 130 plasma features that could be detected and quantified in the GC-MS spectra, we identified contrasting levels of 22 urine and 21 plasma features between AVS patients and control subjects. Following metabolite assignment, we observed significant changes in the concentration of known metabolites in urine (n = 14) and plasma (n = 15) that distinguish the metabolomic profiles of AVS patients from healthy controls. Associations with AVS were replicated in both plasma and urine for about half of these metabolites. Among these, 2-Oxovaleric acid, elaidic acid, myristic acid, palmitic acid, estrone, myo-inositol showed contrasting trends of regulation in the two biofluids. Only trans-Aconitic acid and 2,4-Di-tert-butylphenol showed consistent patterns of regulation in both plasma and urine. These results illustrate the power of metabolomics in identifying potential disease-associated biomarkers and provide a foundation for further studies towards early diagnostic applications in severe heart conditions that may prevent surgery in the elderly.
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页数:18
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共 45 条
[1]   Metabolomic distinction and insights into the pathogenesis of human primary dilated cardiomyopathy [J].
Alexander, Danny ;
Lombardi, Raffaella ;
Rodriguez, Gabriela ;
Mitchell, Matthew M. ;
Marian, Ali J. .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2011, 41 (05) :527-538
[2]   MICROBIOLOGICAL DISSIMILATION OF TRICARBALLYLATE AND TRANS-ACONITATE [J].
ALTEKAR, WW ;
RAGHAVEN.MR .
JOURNAL OF BACTERIOLOGY, 1963, 85 (03) :604-+
[3]   Integration of the human exposome with the human genome to advance medicine [J].
Barouki, Robert ;
Audouze, Karine ;
Coumoul, Xavier ;
Demenais, Florence ;
Gauguier, Dominique .
BIOCHIMIE, 2018, 152 :155-158
[4]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[5]   Distinct Urinary Metabolic Profile of Human Colorectal Cancer [J].
Cheng, Yu ;
Xie, Guoxiang ;
Chen, Tianlu ;
Qiu, Yunping ;
Zou, Xia ;
Zheng, Minhua ;
Tan, Binbin ;
Feng, Bo ;
Dong, Taotao ;
He, Pingang ;
Zhao, Linjing ;
Zhao, Aihua ;
Xu, Lisa X. ;
Zhang, Yan ;
Jia, Wei .
JOURNAL OF PROTEOME RESEARCH, 2012, 11 (02) :1354-1363
[6]   Statistical total correlation spectroscopy:: An exploratory approach for latent biomarker identification from metabolic 1H NMR data sets [J].
Cloarec, O ;
Dumas, ME ;
Craig, A ;
Barton, RH ;
Trygg, J ;
Hudson, J ;
Blancher, C ;
Gauguier, D ;
Lindon, JC ;
Holmes, E ;
Nicholson, J .
ANALYTICAL CHEMISTRY, 2005, 77 (05) :1282-1289
[7]   Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies [J].
de Souza, Russell J. ;
Mente, Andrew ;
Maroleanu, Adriana ;
Cozma, Adrian I. ;
Ha, Vanessa ;
Kishibe, Teruko ;
Uleryk, Elizabeth ;
Budylowski, Patrick ;
Schuenemann, Holger ;
Beyene, Joseph ;
Anand, Sonia S. .
BMJ-BRITISH MEDICAL JOURNAL, 2015, 351
[8]   Metabolomic approach to profile functional and metabolic changes in heart failure [J].
Deidda, Martino ;
Piras, Cristina ;
Dessalvi, Christian Cadeddu ;
Locci, Emanuela ;
Barberini, Luigi ;
Torri, Federica ;
Ascedu, Federica ;
Atzori, Luigi ;
Mercuro, Giuseppe .
JOURNAL OF TRANSLATIONAL MEDICINE, 2015, 13
[9]   Fatty acids linked to cardiovascular mortality are associated with risk factors [J].
Ebbesson, Sven O. E. ;
Voruganti, Venkata S. ;
Higgins, Paul B. ;
Fabsitz, Richard R. ;
Ebbesson, Lars O. ;
Laston, Sandra ;
Harris, William S. ;
Kennish, John ;
Umans, Benjamin D. ;
Wang, Hong ;
Devereux, Richard B. ;
Okin, Peter M. ;
Weissman, Neil J. ;
MacCluer, Jean W. ;
Umans, Jason G. ;
Howard, Barbara V. .
INTERNATIONAL JOURNAL OF CIRCUMPOLAR HEALTH, 2015, 74
[10]   Urinary metabolic signatures of human adiposity [J].
Elliott, Paul ;
Posma, Joram M. ;
Chan, Queenie ;
Garcia-Perez, Isabel ;
Wijeyesekera, Anisha ;
Bictash, Magda ;
Ebbels, Timothy M. D. ;
Ueshima, Hirotsugu ;
Zhao, Liancheng ;
van Horn, Linda ;
Daviglus, Martha ;
Stamler, Jeremiah ;
Holmes, Elaine ;
Nicholson, Jeremy K. .
SCIENCE TRANSLATIONAL MEDICINE, 2015, 7 (285)