TY - JOUR
T1 - Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity
AU - Quercioli, Alessandra
AU - Pataky, Zoltan
AU - Vincenti, Gabriella
AU - Makoundou, Vincent
AU - Di Marzo, Vincenzo
AU - Montecucco, Fabrizio
AU - Carballo, Sebastian
AU - Thomas, Aurlien
AU - Staub, Christian
AU - Steffens, Sabine
AU - Seimbille, Yann
AU - Golay, Alain
AU - Ratib, Osman
AU - Harsch, Elisabetta
AU - MacH, Franois
AU - Schindler, Thomas H.
N1 - Funding Information:
This work was supported by Research Grant 3200B0-122237, Swiss National Science Foundation (SNF), with contributions of the Clinical Research Center, University Hospital and Faculty of Medicine, Geneva and the Louis-Jeantet Foundation, Swiss Heart Foundation, and the Department of Internal Medicine of the University Hospitals of Geneva (Switzerland), and Fellowship Grants from the Novartis Foundation (A.Q.), and the European Society of Cardiology (ESC) and the Italian Society of Cardiology (Societa‘ Italiana di Cardiologia; SIC) (G.V.).
PY - 2011/6
Y1 - 2011/6
N2 - AimsAim 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. Methods and resultsMyocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with 13N-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. Conclusion sIncreased 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.
AB - AimsAim 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. Methods and resultsMyocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with 13N-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. Conclusion sIncreased 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.
KW - blood flow
KW - circulation
KW - coronary disease
KW - endocannabinoids
KW - endothelium
KW - obesity
UR - https://www.scopus.com/pages/publications/79958109354
U2 - 10.1093/eurheartj/ehr029
DO - 10.1093/eurheartj/ehr029
M3 - Article
C2 - 21303779
AN - SCOPUS:79958109354
SN - 0195-668X
VL - 32
SP - 1369
EP - 1378
JO - European heart journal
JF - European heart journal
IS - 11
ER -