Alessandra Quercioli1, Federico Carbone2, Aldo Bonaventura2, Luca Liberale2, Zoltan Pataky3, Aurélien Thomas4, Sébastien Lenglet4, Estelle Lauer4, Alain Golay3, Franco Dallegri5, Vincenzo Di Marzo6, Thomas H Schindler7, Fabrizio Montecucco8. 1. Division of Cardiology, "SS. Antonio e Biagio e Cesare Arrigo" Hospital, 6 via Venezia 16, 15121 Alessandria, Italy. 2. First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy. 3. 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. 4. Unit of Toxicology, CURML, Geneva-Lausanne, CHUV, HUG, rue Michel-Servet 1, 1211 Geneva, Switzerland. 5. 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. 6. Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy. 7. 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. 8. 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.
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 with 13N-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. CONCLUSION: 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.
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 with 13N-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. CONCLUSION: 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: Lea Tischmann; Mathijs Drummen; Peter J Joris; Blandine Gatta-Cherifi; Anne Raben; Mikael Fogelholm; Isabelle Matias; Daniela Cota; Ronald P Mensink; Margriet S Westerterp-Plantenga; Tanja C Adam Journal: Nutrients Date: 2020-05-22 Impact factor: 5.717