Saulnier-Blache, J.S.* ; Wilson, R. ; Klavins, K.* ; Graham, D.* ; Alesutan, I.* ; Kastenmüller, G. ; Wang-Sattler, R. ; Adamski, J. ; Roden, M.* ; Rathmann, W.* ; Seissler, J. ; Meisinger, C. ; Koenig, W.* ; Thiery, J.* ; Suhre, K.* ; Peters, A. ; Kuro-O, M.* ; Lang, F.* ; Dallmann, G.* ; Delles, C.* ; Voelkl, J.* ; Waldenberger, M. ; Bascands, J.-L.* ; Klein, J.* ; Schanstra, J.P.*
Ldlr(-/-) and ApoE(-/-) mice better mimic the human metabolite signature of increased carotid intima media thickness compared to other animal models of cardiovascular disease.
Atherosclerosis 276, 140-147 (2018)
Background and aims: Preclinical experiments on animal models are essential to understand the mechanisms of cardiovascular disease (CVD). Metabolomics allows access to the metabolic perturbations associated with CVD in heart and vessels. Here we assessed which potential animal CVD model most closely mimics the serum metabolite signature of increased carotid intima-media thickness (cIMT) in humans, a clinical parameter widely accepted as a surrogate of CVD.Methods: A targeted mass spectrometry assay was used to quantify and compare a series of blood metabolites between 1362 individuals (KORA F4 cohort) and 5 animal CVD models: ApoE(-/-), Ldlr(-/-), and klotho-hypomorphic mice (kl/kl) and SHRSP rats with or without salt feeding. The metabolite signatures were obtained using linear regressions adjusted for various co-variates.Results: In human, increased cIMT [quartile Q4 vs. Q1] was associated with 26 metabolites (9 acylcarnitines, 2 lysophosphatidylcholines, 9 phosphatidylcholines and 6 sphingomyelins). Acylcarnitines correlated preferentially with serum glucose and creatinine. Phospholipids correlated preferentially with cholesterol (total and LDL). The human signature correlated positively and significantly with Ldlr(-/-) and ApoE(-/-) mice, while correlation with kl/kl mice and SHRP rats was either negative and non-significant. Human and Ldlr(-/-) mice shared 11 significant metabolites displaying the same direction of regulation: 5 phosphatidylcholines, 1 lysophosphatidylcholines, 5 sphingomyelins; ApoE(-/-) mice shared 10.Conclusions: The human cIMT signature was partially mimicked by Ldlr(-/-) and ApoE(-/-) mice. These animal models might help better understand the biochemical and molecular mechanisms involved in the vessel metabolic perturbations associated with, and contributing to metabolic disorders in CVD. (c) 2018 Elsevier B.V. All rights reserved.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Cardiovascular Disease ; Carotid Intima Media Thickness ; Metabolomics ; Animal Models ; Atherosclerosis ; Phospholipids ; Acylcarnitines; Coronary-artery-disease; Spontaneously Hypertensive-rat; Blood-pressure; Chromosome 2; Atherosclerosis; Plasma; Klotho; Calcification; Lipidomics; Genes
Keywords plus
Sprache
Veröffentlichungsjahr
2018
Prepublished im Jahr
HGF-Berichtsjahr
2018
ISSN (print) / ISBN
0021-9150
e-ISSN
1879-1484
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 276,
Heft: ,
Seiten: 140-147
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
Amsterdam
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30202 - Environmental Health
30505 - New Technologies for Biomedical Discoveries
30201 - Metabolic Health
Forschungsfeld(er)
Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e)
G-504091-001
G-503700-001
G-505600-003
G-521500-002
G-504000-006
G-504000-001
G-504090-001
Förderungen
Copyright
Erfassungsdatum
2018-07-25