title: Lipidomic and metabolomic analyses reveal potential plasma biomarkers of early atheromatous plaque formation in hamsters.
abstract: OBJECTIVE
  Atherosclerosis is the main pathological process contributing to cardiovascular disease, with diet being the most important factor involved. Although the lipidome of atheromatous plaque has been studied previously, the use of comparative lipidomics and metabolomics in plasma in early atherogenesis could lead to the discovery of plasma biomarkers that allow not only disease prediction but also measurement of disease progression.
  
  
  RESULTS
  High-throughput techniques, such as liquid chromatography/mass spectrometry, allowed us to compare the circulating and aortic lipidome and plasma metabolome in order to look for new molecular targets involved in atherogenesis. To achieve this objective, we chose the hamster (Mesocricetus auratus) as the best small animal model for diet-induced early atherosclerosis, because its lipoprotein metabolism is similar to that of humans. The results revealed the existence of several, previously unreported, changes in lipid and amino-acid metabolism, the peroxisome proliferator-activated receptor γ pathway, and oxidative and endoplasmic reticulum stress, also involving cell senescence. Furthermore, as a proof of concept in the modelling of dietary influences in atherogenesis, we have measured the effect of a potential anti-atherogenic polyphenol extract on the reported pathways. Our results support a previously unknown role for taurocholic acid as a potential plasma biomarker of early atheromatous plaque formation.
  
  
  CONCLUSIONS
  The use of comparative liquid chromatography/mass spectrometry-based lipidomics and metabolomics allows the discovery of novel pathways in atherogenesis, as well as new potential plasma biomarkers, which could allow us to predict disease in its early stages and measure its progression.
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine, Universitat de Lleida-IRBLleida, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Jové
authors.forename: Victòria
authors.initials: V
authors.lastname: Ayala
authors.forename: Omar
authors.initials: O
authors.lastname: Ramírez-Núñez
authors.forename: José C E
authors.initials: JC
authors.lastname: Serrano
authors.forename: Anna
authors.initials: A
authors.lastname: Cassanyé
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
authors.forename: Antoni
authors.initials: A
authors.lastname: Caimari
authors.forename: Josep M
authors.initials: JM
authors.lastname: Del Bas
authors.forename: Anna
authors.initials: A
authors.lastname: Crescenti
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otín
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D016922:Cellular Senescence; D006224:Cricetinae; D059305:Diet, High-Fat; D057809:HEK293 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008647:Mesocricetus; D055432:Metabolomics / Q000379:methods*; D047495:PPAR gamma / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000175:diagnosis; D013656:Taurocholic Acid / Q000097:blood
chemical_list: D015415:Biomarkers; D008055:Lipids; D047495:PPAR gamma; D010936:Plant Extracts; D013656:Taurocholic Acid; D007703:Peptidyl-Dipeptidase A