title: Plasma palmitoylethanolamide (PEA) as a potential biomarker for impaired coronary function.
abstract: BACKGROUND
  Among endocannabinoid (EC)-related mediators, Oleoyl-ethanolamide (OEA) and Palmitoyl-ethanolamide (PEA), two endogenous PPARα agonists with lipolytic and anti-inflammatory action, respectively, are being actively investigated. Here, we assessed the potential association between plasma levels of PEA and OEA and coronary function in a cohort including normal, overweight, obese, and morbidly obese (MOB) individuals.
  
  
  METHODS
  Myocardial perfusion and endothelium-related myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with13N-ammonia positron emission tomography/computed tomography. OEA and PEA were extracted from human plasma by liquid-liquid extraction, separated by liquid chromatography and quantified by mass spectrometry. Serum levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1) were measured by colorimetric enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Circulating levels of PEA and VCAM-1 were increased in MOB as compared to normal weight subjects. Circulating levels of OEA and PEA were associated with body mass index, but not with adhesion molecules. Increases of PEA levels were associated with and predictive of worsened coronary function in MOB and the overall cohort studied.
  
  
  CONCLUSIONS
  Plasma levels of PEA are increased in MOB patients and associated with coronary dysfunction as a functional precursor of CAD process. Larger trials are needed to confirm PEA as a potential circulating biomarker of coronary dysfunction in both MOB patients and the general population.
authors.affiliation: Division of Cardiology, "SS. Antonio e Biagio e Cesare Arrigo" Hospital, 6 via Venezia 16, 15121 Alessandria, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Quercioli
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Carbone
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Bonaventura
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Liberale
authors.affiliation: Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Pataky
authors.affiliation: Unit of Toxicology, CURML, Geneva-Lausanne, CHUV, HUG, rue Michel-Servet 1, 1211 Geneva, Switzerland.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Unit of Toxicology, CURML, Geneva-Lausanne, CHUV, HUG, rue Michel-Servet 1, 1211 Geneva, Switzerland.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lenglet
authors.affiliation: Unit of Toxicology, CURML, Geneva-Lausanne, CHUV, HUG, rue Michel-Servet 1, 1211 Geneva, Switzerland.
authors.forename: Estelle
authors.initials: E
authors.lastname: Lauer
authors.affiliation: Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Golay
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; IRCCS AOU San Martino-IST, Genova, largo Benzi 10, 16143 Genoa, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Division of Nuclear Medicine, Cardiovascular Section, Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, JHOC 3225, 601 N. Caroline Street, Baltimore, MD 21287, USA; Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Schindler
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; IRCCS AOU San Martino-IST, Genova, largo Benzi 10, 16143 Genoa, Italy; Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 viale Benedetto XV, 16132 Genoa, Italy.. Electronic address: Fabrizio.montecucco@unige.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
mesh_terms: D000577:Amides; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002853:Chromatography, Liquid; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D004983:Ethanolamines / Q000097:blood*; D006801:Humans; D009765:Obesity / Q000097:blood* / Q000150:complications; D010169:Palmitic Acids / Q000097:blood*; D000072078:Positron Emission Tomography Computed Tomography; D012039:Regional Blood Flow / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D000577:Amides; D015415:Biomarkers; D004983:Ethanolamines; D010169:Palmitic Acids; C005958:palmidrol
keywords: Adhesion molecules; Coronary circulation; Endocannabinoid system; OEA; Obesity; PEA