title: Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity.
abstract: OBJECTIVE
  Aim of this study was to evaluate a possible association between endocannabinoid (EC) plasma levels, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and coronary circulatory function in obesity.
  
  
  RESULTS
  Myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with (13)N-ammonia PET/CT. Study participants (n = 77) were divided into three groups based on their body mass index (BMI, kg/m(2)): control group 20 ≤ BMI <25 (n = 21); overweight group, 25 ≤ BMI <30 (n = 26); and obese group, BMI ≥ 30 (n = 30). Anandamide plasma levels, but not 2-AG plasma levels, were significantly elevated in obesity as compared with controls, respectively [0.68 (0.53, 0.78) vs. 0.56 (0.47, 0.66) ng/mL, P = 0.020, and 2.2 (1.21, 4.59) vs. 2.0 (0.80, 5.90) ng/mL, P = 0.806)]. The endothelium-related change in MBF during CPT from rest (ΔMBF) progressively declined in overweight and obese when compared with control group [0.21 (0.10, 0.27) and 0.09 (-0.01, 0.15) vs. 0.26 (0.23, 0.39) mL/g/min; P = 0.010 and P = 0.0001, respectively). Compared with controls, hyperaemic MBFs were significantly lower in overweight and obese individuals [2.39 (1.97, 2.62) vs. 1.98 (1.69, 2.26) and 2.10 (1.76, 2.36); P = 0.007 and P = 0.042, respectively)]. In obese individuals, AEA and 2-AG plasma levels were inversely correlated with ΔMBF to CPT (r = -0.37, P = 0.046 and r = -0.48, P = 0.008) and hyperaemic MBFs (r = -0.38, P = 0.052 and r = -0.45, P = 0.017), respectively.
  
  
  CONCLUSIONS
  Increased EC plasma levels of AEA and 2-AG are associated with coronary circulatory dysfunction in obese individuals. This observation might suggest increases in EC plasma levels as a novel endogenous cardiovascular risk factor in obesity, but needing further investigations.
authors.affiliation: Department of Internal Medicine, Cardiovascular Center, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Quercioli
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Pataky
authors.forename: Gabriella
authors.initials: G
authors.lastname: Vincenti
authors.forename: Vincent
authors.initials: V
authors.lastname: Makoundou
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
authors.forename: Sebastian
authors.initials: S
authors.lastname: Carballo
authors.forename: Aurélien
authors.initials: A
authors.lastname: Thomas
authors.forename: Christian
authors.initials: C
authors.lastname: Staub
authors.forename: Sabine
authors.initials: S
authors.lastname: Steffens
authors.forename: Yann
authors.initials: Y
authors.lastname: Seimbille
authors.forename: Alain
authors.initials: A
authors.lastname: Golay
authors.forename: Osman
authors.initials: O
authors.lastname: Ratib
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Harsch
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Schindler
mesh_terms: D000368:Aged; D001095:Arachidonic Acids / Q000378:metabolism*; D015992:Body Mass Index; D063385:Cannabinoid Receptor Modulators / Q000097:blood*; D016022:Case-Control Studies; D003326:Coronary Circulation / Q000502:physiology*; D003327:Coronary Disease / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D063388:Endocannabinoids; D005260:Female; D005989:Glycerides / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D049268:Positron-Emission Tomography
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; C078814:anandamide