title: Perturbations in fatty acid metabolism and apoptosis are manifested in calcific coronary artery disease: An exploratory lipidomic study.
abstract: BACKGROUND
  Controversy exists concerning the beneficial or harmful effects of the presence of ectopic calcification in the coronary arteries. Additionally, further elucidation of the exact pathophysiological mechanism is needed. In this study, we sought to identify metabolic markers of vascular calcification that could assist in understanding the disease, monitoring its progress and generating hypotheses describing its pathophysiology.
  
  
  METHODS
  Untargeted lipid profiling and complementary modeling strategies were employed to compare serum samples from patients with different levels of calcific coronary artery disease (CCAD) based on their calcium score (CS). Subsequently, patients were divided into three groups: no calcification (NC; CS=0; n=26), mild calcification (MC; CS:1-250; n=27) and severe (SC; CS>250; n=17).
  
  
  RESULTS
  Phosphatidylcholine levels were found to be significantly altered in the disease states (p=0.001-0.04). Specifically, 18-carbon fatty acyl chain (FAC) phosphatidylcholines were detected in lower levels in the SC group, while 20:4 FAC lipid species were detected in higher concentrations. A statistical trend was observed with phosphatidylcholine lipids in the MC group, showing the same tendency as with the SC group. We also observed several sphingomyelin signals present at lower intensities in SC when compared with NC or MC groups (p=0.000001-0.01).
  
  
  CONCLUSIONS
  This is the first lipid profiling study reported in CCAD. Our data demonstrate dysregulations of phosphatidylcholine lipid species, which suggest perturbations in fatty acid elongation/desaturation. The altered levels of the 18-carbon and 20:4 FAC lipids may be indicative of disturbed inflammation homeostasis. The marked sphingomyelin dysregulation in SC is consistent with profound apoptosis as a potential mechanism of CCAD.
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, SW7 2AZ, London, UK.
authors.forename: Panagiotis A
authors.initials: PA
authors.lastname: Vorkas
authors.affiliation: Pharmaceutical Discovery and Life Sciences, Waters Corporation, Milford, MA 01757, USA.
authors.forename: Giorgis
authors.initials: G
authors.lastname: Isaac
authors.affiliation: Department of Public Health and Clinical Medicine, Heart Centre, Umea University, Umea, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Holmgren
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, SW7 2AZ, London, UK.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Want
authors.affiliation: Pharmaceutical Discovery and Life Sciences, Waters Corporation, Milford, MA 01757, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Shockcor
authors.affiliation: Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, SW7 2AZ, London, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Department of Public Health and Clinical Medicine, Heart Centre, Umea University, Umea, Sweden. Electronic address: michael.henein@umu.se.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Henein
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002114:Calcinosis / Q000175:diagnosis / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000378:metabolism*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000097:blood*; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D061330:Multidetector Computed Tomography
chemical_list: D005227:Fatty Acids; D008055:Lipids
keywords: Apoptosis; Calcification; Fatty acid; Lipidomics; Metabolomics; Metabonomics